Has bovine somatotropin (BST) an effect upon drug disposition? Comparative studies in goats and cattle with sulphadimidine and antipyrine after parenteral administration of BST,zeranol and proligestone

Daily subcutaneous BST injection in lactating cows, bulls and castrated male dwarf goats did not induce significant changes in the pharmacokinetic parameters of antipyrine (AP) and sulphadimidine (SDD). Similarly, no changes were obtained after injection of slow-release BST formulations in lactating cows and non-lactating female goats. In contrast to androgenic hormones, both zeranol and proligestone had no effect upon the disposition of AP and SDD, although both synthetic hormones did induce enhanced plasma somatotropin concentrations. In goats, metabolic effects induced by zeranol and BST included significant reductions in plasma urea values, whereas plasma creatinine levels were somewhat lower after daily BST administration.     

Effects of organic and mineral fertilizer inputs on maize yield and soil chemical properties in a maize cropping system in Meru South District, Kenya

Soil nutrient depletion as a result of continuous cultivation of soils without adequate addition of external inputs is a major challenge in the highlands of Kenya. An experiment was set up in Meru South District, Kenya in 2000 to investigate the effects of different soil-incorporated organic (manure, Tithonia diversifolia, Calliandra calothyrsus, Leucaena leucocephala) and mineral fertilizer inputs on maize yield, and soil chemical properties over seven seasons. On average, tithonia treatments (with or without half recommended rate of mineral fertilizer) gave the highest grain yield (5.5 and 5.4 Mg ha⁻¹ respectively) while the control treatment gave the lowest yield (1.5 Mg ha⁻¹). After 2 years of trial implementation, total soil carbon and nitrogen contents were improved with the application of organic residues, and manure in particular improved soil calcium content. Results of the economic analysis indicated that on average across the seven seasons, tithonia with half recommended rate of mineral fertilizer treatment recorded the highest net benefit (USD 787 ha⁻¹) while the control recorded the lowest (USD 272 ha⁻¹). However, returns to labor or benefit-cost ratios were in most cases not significantly improved when organic materials were used.     

Polypeptide composition of fraction 1 protein from parasexual hybrid plants in the genus Nicotiana

Analysis of the subunit polypeptide composition of Fraction 1 proteins gives information on the expression of both nuclear and chloroplast genomes; the large subunits of the protein are coded by chloroplast DNA, whereas the small subunits are coded by nuclear DNA. Fraction 1 protein isolated from the leaves of parasexual hybrid plants derived from the fusion of protoplasts of Nicotiana glauca and N. langsdorffii contains the small subunit polypeptides of both parent species and the large subunit polypeptides of only N. glauca. Fraction 1 protein isolated from the leaves of a hybrid plant obtained after the uptake of chloroplasts of N. suaveolens by protoplasts of white tissue of a variegating mutant of N. tabacum contains the large subunit polypeptides of both N. suaveolens and N. tabacum, as well as the small subunit polypeptides of both these species.     

Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Design and chemical synthesis of a homogeneous polymer-modified erythropoiesis protein

We report the design and total chemical synthesis of "synthetic erythropoiesis protein" (SEP), a 51-kilodalton protein-polymer construct consisting of a 166-amino-acid polypeptide chain and two covalently attached, branched, and monodisperse polymer moieties that are negatively charged. The ability to control the chemistry allowed us to synthesize a macromolecule of precisely defined covalent structure. SEP was homogeneous as shown by high-resolution analytical techniques, with a mass of 50,825 +/-10 daltons by electrospray mass spectrometry, and with a pI of 5.0. In cell and animal assays for erythropoiesis, SEP displayed potent biological activity and had significantly prolonged duration of action in vivo. These chemical methods are a powerful tool in the rational design of protein constructs with potential therapeutic applications.     

Self-trapping of dark incoherent light beams

"Dark beams" are nonuniform optical beams that contain either a one-dimensional (1D) dark stripe or a two-dimensional (2D) dark hole resulting from a phase singularity or an amplitude depression in their optical field. Thus far, self-trapped dark beams (dark solitons) have been observed using coherent light only. Here, self-trapped dark incoherent light beams (self-trapped dark incoherent wavepackets) were observed. Both dark stripes and dark holes nested in a broad partially spatially incoherent wavefront were self-trapped to form dark solitons in a host photorefractive medium. These self-trapped 1D and 2D dark beams induced refractive-index changes akin to planar and circular dielectric waveguides. The experiments introduce the possibility of controlling high-power coherent laser beams with low-power incoherent light sources such as light emitting diodes.     

Role of T-bet in commitment of TH1 cells before IL-12-dependent selection

How cytokines control differentiation of helper T (TH) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-gamma (IFN-gamma) alleles and by inducing IL-12 receptor beta2 expression. Subsequently, it appears that IL-12/STAT4 serves two essential functions in the development of TH1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-gamma synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.     

Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix

BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways.     

Congenital porto-systemic shunts in sixteen dogs and three cats

Congenital porto-systemic shunts in sixteen dogs and three cats are described. A major symptom was hepato-encephalopathy. In most cases diagnosis was based on elevated venous ammonia levels, abnormal ammonia tolerance and results of operative mesenteric portography. Clinical signs, laboratory findings, results of portography, and pathologic findings in the liver and the central nervous system are described. A diagnostic schedule is proposed to aid in recognition of this syndrome.