The rabbit alpha-like globin gene cluster is polymorphic both in the sizes of BamHI fragments and in the numbers of duplicated sets of genes

The alpha-like globin gene cluster in rabbits contains embryonic zeta- globin genes, an adult alpha-globin gene, and theta-globin genes of undetermined function. The basic arrangement of genes, deduced from analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3'. However, the pattern of restriction fragments containing zeta- and theta-globin genes varies among individual rabbits. Analysis of BamHI fragments of genomic DNA from 24 New Zealand white rabbits revealed eight different patterns of fragments containing zeta-globin genes. The large BamHI fragments containing genes zeta 0 and zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary in size. In contrast to this constancy in the size of the restriction fragments, the copy number of the zeta 2 and zeta 3 genes does vary among different rabbits. No length polymorphism was detected in the BamHI fragments containing the theta-globin genes, but again the copy number varies for restriction fragments containing the theta 2 gene. The alpha 1- and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI fragment. The combined data from hybridization with both zeta and theta probes shows that the BamHI cleavage pattern does not vary within the region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern genomic blot-hybridization patterns for the progeny of parental rabbits with different zeta-globin gene patterns shows that the polymorphic patterns are inherited in a Mendelian fashion. Two different haplotypes have been mapped based on the genomic blot-hybridization data. The variation in the alpha-like globin gene cluster in the rabbit population results both from differences in the copy number of the duplication block containing the zeta-zeta-theta gene set and from the presence or absence of polymorphic BamHI sites.      

Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium

Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel.     

Pomphorhynchus laevis (Müller) in the flounder, Platichthys flesus L., in the tidal River Thames: population structure, microhabitat utilization and reproductive status in the field and under conditions of controlled salinity

The infection of R. Thames flounders, Platichthys flesus L., at Fulham by the acanthocephalan parasite Pomphorhynchus laevix (Müller) is described in terms of parasite population structure, life-cycle organization, reproductive biology and host microhabitat utilization. The parasites demonstrated 100% prevalence in this tidal but essentially freshwater locality (intestinal intensity 34.47) and were overdispersed in the flounder population (variance/mean ratio = 10.39, k= 1.04). Overall about 11% of the worms occurred in peritoneal cavity sites, the remainder being firmly attached to the gut wall in the posterior region of the intestine and rectum. The P. laevis populations were reproductively active, demonstrating that the flounder acts as a significant final host in this locality. Viable larval stages were identified in Gammarus zaddachi Sexton, a predominantly estuarine amphipod, indicating that P. laevis is likely to be able to complete its life cycle at Fulham. Over half the female parasites examined were gravid and many of the non-gravid worms were inseminated but had not yet started egg production. The proportion of females gravid, the number of ovarian balls and the number of eggs in gravid females was seen to increase with worm size. Both the identity of the intermediate host and the reproductive status of P. laevis in the Thames flounders differ from the Pomphorhynchus/flounder system studied by Kennedy (1984) in the R. Avon, suggesting that the two P. laevis populations may belong at least to discrete subspecies or strains. Parasites in flounders maintained under laboratory conditions in fresh water, 50% sea water and 100% sea water showed similar population, microhabitat and reproductive characteristics to those observed in the field. This suggests that increased salinity has a negligible effect on established parasites in the short term, and therefore that salinity may not form a barrier to the survival and dispersal of the R. Thames parasite when the flounders return to sea.     

The role of type-IIIStreptococcus agalactiae extracellular type-specific antigen in mouse virulence enhancement

The adult mouse model was employed to examine the mechanism of virulence enhancement by the extracellular type-specific antigen (ETSA) of type-IIIStreptococcus agalactiae. Intraperitoneal injection of ETSA along with the infecting strain lowered the LD₅₀ value forS. agalactiae and allowed for a more rapid proliferation of the organisms as opposed to that caused by the presence of a nonspecific dextran. The ETSA did not hinder recruitment of peritoneal exudate cells (PEC) into the peritoneal cavity as has been shown with capsular antigens of other bacteria. Chemiluminescent responses of mouse resident PEC demonstrated that these cells could render a respiratory burst when exposed to type-IIIS. agalactiae in the absence of complement and/or type-specific antibody. If the mouse PEC were exposed to ETSA before phagocytosis was attempted, however, ingestion of the type-III group-B streptococci was reduced. ETSA did not affect the viability of the PEC as determined by trypan blue exclusion. These results indicate that the ETSA can affect mouse PEC in an unidentified manner, thus rendering them less capable of ingesting and/or kiling type-IIIS. agalactiae.     

Association between pygmy right whales (Caperea marginata) and areas of high marine productivity off Australia and New Zealand

Abstract

Opportunistic sightings and strandings of Caperea marginata (n=196) from the vicinity of Australia and New Zealand (1884 to early 2007) were used to relate geographic and temporal patterns to oceanographic and broad-scale climatic variability. Records were not uniformly distributed along the coast and more (69%) were from Australia than New Zealand. Seven coastal whale ‘hotspots’ were identified which accounted for 61% of records with locality data. Half of the hotspot records were from southeast (37) and northwest (20) Tasmania—others each had 9–15 events. Upwelling and/or high zooplankton abundance has been documented near all whale hotspots. Records of C. marginata occurred in all months, with 75% in spring and summer. Inter-annual variability showed broad agreement between increased whale records (usually in spring/summer) and strongly positive ‘Niño 3.4’ during 1980–1995 but not thereafter. Coastal upwelling and productivity increase during climatic phenomena such as El Niño and are likely to be quickly beneficial to plankton-feeding whales such as C. marginata.     

Regulation of early events in chromosome replication

Eukaryotic genomes are replicated from large numbers of replication origins distributed on multiple chromosomes. The activity of these origins must be coordinated so that the entire genome is efficiently and accurately replicated yet no region of the genome is ever replicated more than once. The past decade has seen significant advances in understanding how the initiation of DNA replication is regulated by key cell-cycle regulators, including the cyclin dependent kinases (CDKs) and the anaphase promoting complex/cyclosome (APC/C). The assembly of essential prereplicative complexes (pre-RCs) at origins only occurs when CDK activity is low and APC/C activity is high. Origin firing, however, can only occur when the APC/C is inactivated and CDKs become active. This two step mechanism ensures that no origin can fire more than once in a cell cycle. In all eukaryotes tested, CDKs can contribute to the inhibition of pre-RC assembly. This inhibition is characterised both by high degrees of redundancy and evolutionary plasticity. Geminin plays a crucial role in inhibiting licensing in metazoans and, like cyclins, is inactivated by the APC/C. Strategies involved in preventing re-replication in different organisms will be discussed.     

Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies.