Modelling of the disulphide-swapped isomer of human insulin-like growth factor-1: implications for receptor binding.

Insulin-like growth factor-1 (IGF-1) is a serum protein which unexpectedly folds to yield two stable tertiary structures with different disulphide connectivities; native IGF-1 [18-61,6-48,47-52] and IGF-1 swap [18-61,6-47, 48-52]. Here we demonstrate in detail the biological properties of recombinant human native IGF-1 and IGF-1 swap secreted from Saccharomyces cerevisiae. IGF-1 swap had a approximately 30 fold loss in affinity for the IGF-1 receptor overexpressed on BHK cells compared with native IGF-1.The parallel increase in dose required to induce negative cooperativity together with the parallel loss in mitogenicity in NIH 3T3 cells implies that disruption of the IGF-1 receptor binding interaction rather than restriction of a post-binding conformational change is responsible for the reduction in biological activity of IGF-1 swap. Interestingly, the affinity of IGF-1 swap for the insulin receptor was approximately 200 fold lower than that of native IGF-1 indicating that the binding surface complementary to the insulin receptor (or the ability to attain it) is disturbed to a greater extent than that to the IGF-1 receptor. A 1.0 ns high-temperature molecular dynamics study of the local energy landscape of IGF-1 swap resulted in uncoiling of the first A-region alpha-helix and a rearrangement in the relative orientation of the A- and B-regions. The model of IGF-1 swap is structurally homologous to the NMR structure of insulin swap and CD spectra consistent with the model are presented. However, in the model of IGF-1 swap the C-region has filled the space where the first A-region alpha-helix has uncoiled and this may be hindering interaction of Val44 with the second insulin receptor binding pocket.     

Comparison of two techniques for quantifying environmental contaminants in human serum

Peak area matching and linear regression were used to quantify eight chlorinated pesticides and polychlorinated biphenyls (as Aroclor 1260) in human serum. There are no statistically significant differences in data obtained by these two quantifying techniques which were indicated by the paired t-test. For chlorinated pesticides, p = 0.053-0.62, and for polychlorinated biphenyls (as Aroclor 1260), p = 0.64. Analyte residues for the chlorinated pesticides ranged from 0.5 ppb for hexachlorobenzene (HCB) to 186 ppb for dichlorodiphenyldichloroethylene (DDE). Analyte residues for the polychlorinated biphenyls (as Aroclor 1260) ranged from 5-114 ppb. The absolute mean percent difference between the two quantifying techniques ranged from 0.06% for DDE to 8.06% for dieldrin (HEOD) among the chlorinated pesticides. The absolute mean percent difference between the two quantifying techniques for the polychlorinated biphenyls (as Aroclor 1260) was 3.4%. Peak area matching and linear regression were found to be comparable for quantifying these environmental residues in serum when the following conditions apply: 1) the concentration of the chlorinated pesticides is greater than or equal to 0.5 ppb (e.g., HCB, hexachlorocyclohexane (HCCH), oxychlordane (OC), heptachlor epoxide (HE), transnonachlor (TN), HEOD, and dichlorodiphenyltrichloroethane (DDT); 2) the concentration of the chlorinated pesticide is greater than or equal to 3 ppb (e.g., DDE); and 3) the total concentration of polychlorinated biphenyls (e.g., as Aroclor 1260) is greater than or equal to 5 ppb.     

Isolation of Actinomycetes synthesizing proteases with thrombolytic activity

Proteases with the thrombolytic activity were studied in 212 strains of actinomycetes isolated from different soils of the Soviet Union. The cultures belonged to the genera Micromonospora, Nocardia and Streptomyces. Proteases were synthesized by 41% of the studied actinomycetes and some of their strains completely dissolved in vitro artificially obtained blood thrombi within 120-240 min. In the Streptomyces genus, more active strains were found in the groups Flavus, Fradia and Globisporus. The groups Olivaceus, Violaceus and Viridis had less active strains.     

X-ray semeiotics of sclerosis of the prostate

Infravesical obstruction in 300 male patients was determined by prostatic sclerosis (PS). PS is a polyetiological disease developing more frequently as a result of prostatitis, autoimmune, allergic and congestive factors. Sclerosis and shriveling of the gland cause topographo-anatomic changes in the infravesical area, well revealed during a combined roentgeno-urological study. Direct signs of PS are the following: stenosis, deformity and shortening of the prostatic part of the urethra, a high position of the lower outline of the bladder resembling braces over the public symphysis; indirect signs: change of the bladder shape, megacyst, trabecular mucosa and diverticulosis, congestion in the upper urinary tracts, uni- or bilateral urethero-hydronephrosis.     

The effect of administering corticoliberin into the striatum on the open-field and shuttle-box behaviors of KHA and KLA strain rats]

The effects of corticotropin-releasing hormone (CRH) injected into the dorsal neostriatum on the open-field and shuttle-box behavior were studied in rats with high (Koltushi high avoidance, KHA) and low (Koltushi low avoidance, KLA) capability for avoidance learning. The effects of this hormone on the behavior of these rat strains were different. In KLA rats with passive strategy of behavior the CRH injection led to a rapid locomotor activation in the open field, while the rats with active behavioral strategy (KHA) reacted to the injection by a significant decrease in locomotion and change for the passive mode of behavior. The same CRH effects on locomotion were obtained in the shuttle-box experiments. Moreover, in the KLA rats the neurohormone injection resulted in an improvement of avoidance learning in contrast to the KHA rats, in which CRH substantially impaired avoidance learning. The obtained evidence is discussed in terms of the important role of striatal CRH in the choice of behavioral strategy in stress.     

Moult in Black-browed and Grey-headed Albatrosses Diomedea melanophris and D. chrysostoma

We recorded the age of individual wing and tail feathers of Black-browed and Grey-headed Albatrosses Diomedea melanophris and D. chrysostoma of known age and breeding status at Bird Island, South Georgia. Breeders and non-breeders of both species moult their rectrices annually. Non-breeders moult primaries biennially. In the first year of a cycle, the outer three and some inner primaries are moulted descendantly; in the next year the inner primaries are moulted ascendantly, starting from primary seven. There is a general progression to moulting equal numbers of primaries in each half of the cycle by the time breeding starts at about 10 years of age. Grey-headed Albatrosses usually moult fewer primaries than Black-browed Albatrosses, particularly as 3-year-olds, when they undertake substantial plumage change in body moult. Most secondaries in Black-browed Albatrosses have been replaced once by age 4 years. Breeding Black-browed Albatrosses continue the moult pattern established as immatures whether they fail or not, as do failed Grey-headed Albatrosses. Successful Grey-headed Albatrosses, which breed again 16 months later, moult their three innermost primaries after breeding in the remainder of the current year and, after a period when moult is interrupted, renew the remaining primaries the following year. Comparisons between species and between failed and successful birds within species indicate that moult rate is not closely linked to the length of the interval between breeding attempts. Interspecies differences are better explained by breeding latitude, with tropical albatrosses moulting twice as fast as sub-Antarctic species, possibly reflecting food availability outside the breeding season.     

Further studies on the occurrence of freshwater Microturbellaria in the British Isles

Five new British records of freshwater Microturbellaria are illustrated: Gieysztoria infundibuliformis, Castrada lanceola, Castrada neocomensis, Castrada viridis and Strongylostoma elongatum. These species together with a new species, Macrostomum johni described by Young (1972), are woven into the fabric of the existing key for the group (Young, 1970). All six species were recorded from the littoral zone of lakes in Caernarvonshire, N. Wales. The times of the recordings are indicated.