Analysis of the demersal community of fish and cephalopods on the Agulhas Bank, South Africa

The demersal fish and cephalopod communities of the continental shelf and upper slope from 17 to 395m deep were studied during five annual cruises between Cape Agulhas and Port Alfred, South Africa. The cruises showed a consistent pattern of an inshore community (<100m), a shelf community ( c . 90–190m) and a shelf-edge/upper slope fauna (>200m). These groups were identified by dendrograms and multidimensional scaling cluster analysis, which supported on-board observations of catch variation with depth. Although the boundaries are not clearly defined, examination of physical features at the clustered stations suggests that depth, temperature and, to a lesser extent, oxygen concentration are important in the grouping. Occasional, apparently anomalous associations of inshore stations suggested that water temperature and oxygen may over-ride the normal depth distributions of the species groups. This intimates that patterns offish and cephalopod distribution may be dynamic and in part related to the physical parameters of the water body.     

Principles and pitfalls in designing site-directed peptide ligands

An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallo-graphically refined structures of 14 peptide–protein complexes at 2.7 Å resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change inconformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program anend-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligandswere diffused into preexisting crystals. In sucha large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints. © 1993 Wiley-Liss, Inc.     

Testis size,epididymis weight,and sperm competition in rhesus macaques

The intensity of sperm competition is often measured using the gonadosomatic index (testes/body weight). But sperm competition could be mediated more by size of the epididymis than by size of the testicles, and little information is available on the relationship between testicular and epididymal size. We found that both organs were positively correlated in size among male rhesus macaques. Body weight accounted for over 70% of the variance in testicle size and volumetric estimates of testicle size accurately reflected testicle weight. We conclude that methods for ascertaining testicle size are accurate, but the covariation in size between testicles and epididymis will hamper understanding of the physiological mechanisms involved in sperm competition in primates. © 1993 Wiley-Liss, Inc.     

Rapid activation of astrocyte-specific expression of GFAP-lacZ transgene by focal injury

Astrocytes form a key cellular component of the central nervous system. They respond vigorously to diverse neurologic insults by undergoing hypertrophy and increasing expression of the glial fibrillary acidic protein (GFAP) gene, but their functions are largely unknown. To analyze astrocytes in vivo we constructed a transgenic vector from GFAP gene sequences and monitored its efficiency by fusing it to lacZ. Injection of the GFAP-lacZ hybrid gene into the germline of mice yielded six different lines of transgenic mice. In all lines the expression of lacZ was astrocyte-specific. In unmanipulated transgenic animals beta-galactosidase activity was much more prominent in astrocytes of the hippocampal formation, selected white matter tracts, and glial limitans than in astrocytes of other areas. This pattern of expression illustrates the physiologic heterogeneity of astrocytes and probably reflects differences in functional demands placed on these cells in different brain regions. Upmodulation of transgene expression was used to determine the time frame within which astroglial activation and increased GFAP gene expression occur following a neurologic insult. Induction of GFAP-lacZ expression was detectable within 1 hour after focal mechanical trauma. This demonstrates that the response of astrocytes to neurologic injury is very rapid and implies that these cells could fulfill important early functions in wound healing within the central nervous system.     

Biochemical mechanisms of resistance to a new antineoplastic drug CRC 680578 from the nitrosourea class]

The biochemical mechanisms of resistance to CRC 680578, a new antitumour chloroethylnitrosourea alpha-amino acid derivative, were studied. Alterations in DNA, RNA and protein syntheses, SH-group content, drug efflux, activities of replicative and repair enzymes, such as ribonucleotide reductase, thymidine kinase, O6-alkylguanine-DNA-alkyltransferase and DNA polymerases alpha and beta and damages of the DNA secondary structure were investigated in sensitive and resistant to CRC 680578 leukemia L1210 cells. It was found that the total SH-group number in drug-resistant cells was increased (about 1.3-fold in comparison with sensitive cells) which seems to be due to the mechanisms of drug resistance. CHC 680578 induced less pronounced inhibition and more rapid restoration of DNA and RNA synthesis in resistant cells. No differences between the ribonucleotide reductase and thymidine kinase activities were found either in intact cells of the both strains or after drug administration. The efficiency of repair of DNA chloroethyl adducts by O6-alkylguanine-DNA-alkyltransferase in leukemia cells of various sensitivity was found to be identical. The differences in enzyme activities in intact cells of the both strains were insignificant. It was supposed that factors other than changes in the level of O6-alkylguanine-DNA-alkyltransferase in leukemia cells may be responsible for the resistance to CRC 680578. The increase in the levels of DNA polymerase alpha and, especially, of DNA polymerase beta, in sensitive (but not resistant) mouse leukemia cells 48 hours after drug administration is though to define the mechanism of resistance to the new antitumour agent CHC 680578.     

The potential value of CA125 as a tumour marker in small volume, non-evaluable epithelial ovarian cancer.

Seventy four consecutive patients with epithelial ovarian cancer have been followed up longitudinally with serial serum CA125 for up to 48 months. From this database, the CA125 changes in small volume disease have been evaluated. For long term complete responders (n = 12), the mean plateau level of CA125 was 7.2 U/ml (95% confidence interval; 5.6 to 9.2 U/ml). The natural half-life of CA125 at 5.1 days (range 3.8 to 7 days) was calculated from five patients with Stage I and II disease who underwent complete surgical excision. A mean lead time of 99 days (range 14 to 255 days) was demonstrated between marker detection of disease progression and clinically apparent progressive disease in 12 out of 13 patients (92%) who relapsed after chemotherapy induced complete remission. The threshold of tumour volume detection with CA125 is unlikely to be determined by an arbitrary cut-off level. The kinetics of CA125 provide more useful information and the potential to define complete response or indeed cure with CA125 parameters requires further investigation.     

Non-motor microtubule-associated proteins.

Cloning of primary sequences has generated information on the structures of the non-motor microtubule-associated proteins and their relationship to one another. Questions about how classes of microtubule-associated proteins interact are starting to be addressed in vitro and, in vivo, tests of function are being pursued using a variety of cellular and molecular biological strategies.