Microfibril-associated Glycoprotein 2 (MAGP2) Loss of Function Has Pleiotropic Effects in Vivo

Microfibril-associated glycoprotein (MAGP) 1 and 2 are evolutionarily related but structurally divergent proteins that are components of microfibrils of the extracellular matrix. Using mice with a targeted inactivation of Mfap5, the gene for MAGP2 protein, we demonstrate that MAGPs have shared as well as unique functions in vivo. Mfap5^−/− mice appear grossly normal, are fertile, and have no reduction in life span. Cardiopulmonary development is typical. The animals are normotensive and have vascular compliance comparable with age-matched wild-type mice, which is indicative of normal, functional elastic fibers. Loss of MAGP2 alone does not significantly alter bone mass or architecture, and loss of MAGP2 in tandem with loss of MAGP1 does not exacerbate MAGP1-dependent osteopenia. MAGP2-deficient mice are neutropenic, which contrasts with monocytopenia described in MAGP1-deficient animals. This suggests that MAGP1 and MAGP2 have discrete functions in hematopoiesis. In the cardiovascular system, MAGP1;MAGP2 double knockout mice (Mfap2^−/−;Mfap5^−/−) show age-dependent aortic dilation. These findings indicate that MAGPs have shared primary functions in maintaining large vessel integrity. In solid phase binding assays, MAGP2 binds active TGFβ1, TGFβ2, and BMP2. Together, these data demonstrate that loss of MAGP2 expression in vivo has pleiotropic effects potentially related to the ability of MAGP2 to regulate growth factors or participate in cell signaling.     

Founding Pioneers of IVF: Independent innovative researchers generating livebirths within 4 years of the first birth

In this 40th anniversary year of the first IVF live birth, it is pertinent to look at all those teams endeavouring to generate live births from this unique technology and who succeeded within 4 years of the first. There were 9 teams who achieved this and a further 3 who were successful soon after, by the end of 1982. This historical review is compiled by 2 authors who were actively engaged in the field of IVF at the time of the first birth and who have remained active in Reproductive Medicine throughout their professional lives. They bring intimate and relevant knowledge of those pioneer researchers from the early years who can be classified as the "Founding Pioneers" of IVF.     

Replication slippage may cause parallel evolution in the secondary structures of mitochondrial transfer RNAs

Presence of the dihydrouridine (D) stem in the mitochondrial cysteine tRNA is unusually variable among lepidosaurian reptiles. Phylogenetic and comparative analyses of cysteine tRNA gene sequences identify eight parallel losses of the D-stem, resulting in D-arm replacement loops. Sampling within the monophyletic Acrodonta provides no evidence for reversal. Slipped-strand mispairing of noncontiguous repeated sequences during replication or direct replication slippage can explain repeats observed within cysteine tRNAs that contain a D-arm replacement loop. These two mechanisms involving replication slippage can account for the loss of the cysteine tRNA D-stem in several lepidosaurian lineages, and may represent general mechanisms by which the secondary structures of mitochondrial tRNAs are altered.      

Measurement of cytochrome P4501A induction in dab (Limanda limanda) and other teleosts with species-specific cDNA probes: isolation and characterisation of dab cDNA and its use in expression studies with β-naphthoflavone-treated fish

Induction of cytochrome P4501A (CYP1A) in fish is an important biomarker in marine monitoring programmes but a number of factors complicate interpretation of data based on catalytic activity. To provide additional analytical tools, we have cloned and sequenced entire (dab) and partial cDNAs (flounder, turbot, sand eel) from several fish species. A detailed analysis comparing the new sequences to those on the database (13 sequences) is presented and identifies an invariant, teleost-specific sequence (195-IVVSVANVICGMCFGRRYDH-214) which might be the basis for production of a species cross-reactive antibody. Northern and slot blots of fish RNA (sand eel, plaice, turbot, flounder and dab) showed extensive cross-species hybridisation with each of the cDNAs (sand eel, plaice, turbot, flounder and dab). The exception was turbot RNA, which only gave adequate hybridisation when the turbot probe was used. Attempts to normalise the hybridisation data to GAPDH mRNA were not satisfactory since there were significant species differences in expression of this gene and expression was suppressed (20–40%) by β-naphthoflavone treatment. The CYP1A probes indicated induction levels relative to untreated dab of: plaice (five-fold); turbot (12-fold); flounder (12-fold); and dab (10-fold). The study demonstrates the relative ease with which species-specific molecular probes can be generated and used.     

Selective induction of labour following administration of an oral prostaglandin E2 0.5 mg tablet hourly

Induction of labour was performed on 20 patients with favourable induction features by amniotomy and administration of a fixed dose of 0.5 mg of prostaglandin E₂ (PGE₂) hourly. Effective uterine action resulted in a mean time to delivery of 6 hrs 57 mins in primagravid patients and 4 hrs 40 mins in multigravid subjects. In two patients an intravenous oxytocin infusion was used to assist labour. There were no significant maternal or fetal side effects.     

Salt hardiness and dye reduction by potato tissue and mitochondrial fractions as influenced by previous storage of the tubers

Oxygen uptake and tetrazolium reduction occurred at higher rates in discs from potato tubers (Solanum tuberosum L.) stored at 0° than in discs from tubers stored at 12.8°. Tetrazolium reduction was at a higher rate in mitochondrial fractions from tubers stored at 0° than in mitochondrial fractions from tubers stored at 12.8°. These physiological activities were more resistant to hypertonic KCl treatments in tissue and mitochondrial fractions from tubers stored at 0° than in tissue and mitochondrial fractions from tubers stored at 12.8°. Inhibition of O₂ uptake and tetrazolium reduction progressively increased with increasing concentrations of KCl for tissue and mitochondrial fractions from tubers stored at 0 and 12.8°, but inhibition was more severe and occurred at lower concentrations of KCl for the material from tubers stored at 12.8°. Tissue from tubers stored at 0° was at the same time more sensitive to hypotonic solutions and more resistant to hypertonic solutions than corresponding tissue from tubers stored at 12.8°. Adaptive changes brought on in the tubers by the stress of cold storage were demonstrated in the discs and mitochondrial fractions prepared from cold-stored tubers.