Cardiovascular actions of the venom from the Irukandji (Carukia barnesi) jellyfish: Effects in human, rat and guinea-pig tissues in vitro and in pigs in vivo

1. We have investigated the cardiovascular pharmacology of the crude venom extract (CVE) from the potentially lethal, very small carybdeid jellyfish Carukia barnesi, in rat, guinea-pig and human isolated tissues and anaesthetized piglets. 2. In rat and guinea-pig isolated right atria, CVE (0.1-10 mu g/mL) caused tachycardia in the presence of atropine (I mu mol/L), a response almost completely abolished by pretreatment with tetrodotoxin (TTX; 0.1 mu mol/L). In paced left atria from guinea-pig or rat, CVE (0.1-3 mu g/mL) caused a positive inotropic response in the presence of atropine (1 mu mol/L). 3. In rat mesenteric small arteries, CVE (0.1-30 mu g/mL) caused concentration-dependent contractions that were unaffected by 0.1 mu mol/L TTX, 0.3 mu mol/L prazosin or 0.1 mu mol/L co-conotoxin GVIA. 4. Neither the rat right atria tachycardic response nor the contraction of rat mesenteric arteries to CVE were affected by the presence of box jellyfish (Chironex fleckeri) antivenom (92.6 units/mL). 5. In human isolated driven right atrial trabeculae muscle strips, CVE (10 mu g/mL) tended to cause an initial fall, followed by a more sustained increase, in contractile force. In the presence of atropine (I mu mol/L), CVE only caused a positive inotropic response. In separate experiments in the, presence of propranolol (0.2 mu mol/L), the negative inotropic effect of CVE was enhanced, whereas the positive inotropic response was markedly decreased. 6. In anaesthetized piglets, CVE (67 mu g/kg, i.v.) caused sustained tachycardia and systemic and pulmonary hypertension. Venous blood samples demonstrated a marked elevation in circulating levels of noradrenaline and adrenaline. 7. We conclude that C. barnesi venom may contain a neural sodium channel activator (blocked by TTX) that, in isolated atrial tissue (and in vivo), causes the release of transmitter (and circulating) catecholamines. The venom may also contain a 'direct' vasoconstrictor component. These observations explain, at least in part, the clinical features of the potentially deadly Irukandji syndrome.

The medical zoologist - Ronald Vernon Southcott

Dr Ronald Vernon Southcott (1918–1998) was amongst the greatest of the Australian doctor-naturalists. His toxinological contributions included the description and naming of the box-jellyfish, Chironex fleckeri, the first definitive study (1950–1957) of the toxinology, taxonomy and biology of Australian scorpions; and the first observations in Australia of the introduced fiddleback spider, Loxosceles. His research into the medical effects of toxic fungi, poisonous plants and Australian insects was extensive. He was a founding member of the International Society on Toxinology and served on the Toxicon Editorial Board for more than 30 years. He also made extensive contributions to acarology, and to the taxonomy of mites, specifically the sub-families and genera of the Erythraeoidea. This prodigious output was achieved by one who, with the exception of war service (1942–1946), almost never travelled outside South Australia, was almost entirely self-funded and worked from his home laboratory. With Dr. P.D. Scott and C.J. Glover, he was also the authority on the fish of South Australia. Dr. Southcott was also a medical epidemiologist and senior medical administrator (1949–1978) with the Australian Commonwealth Department of Veterans’ Affairs. He served for 30 years as an Honorary Consultant in Toxicology to the Adelaide Children's Hospital. As a zoologist and botanist of astounding breadth, he worked indefatigably in a voluntary capacity for the South Australian Museum, of which he was Museum Board Chairman from 1974 to 1982. In the pantheon of the great doctor-naturalists who have worked in Australia, he stands with Robert Brown and Thomas Lane Bancroft.

Self-regulatory behaviors in children with Down syndrome and typically developing children measured using the Goodman Lock Box

Self-regulation has been identified as an area of difficulty for those with mental retardation. The Goodman Lock Box provides measures of two critical aspects of self-regulation-planfulness and maintenance of goal-directed behavior. In this study, the Lock Box performance of 25 children with Down syndrome was compared with that of 43 typically developing children, matched for mental age (24-36 months). Children in both groups showed similar levels of competence, planfulness and distractibility. However, children with Down syndrome displayed more task-avoidant behavior. Some issues related to the measurements obtained from the Lock Box are raised. (C) 2003 Elsevier Science Ltd. All rights reserved.

A role for the GCC-box in jasmonate-mediated activation of the PDF1.2 gene of arabidopsis

The PDF1.2 gene of Arabidopsis encoding a plant defensin is commonly used as a marker for characterization of the jasmonate-dependent defense responses. Here, using PDF1.2 promoter-deletion lines linked to the beta-glucoronidase-reporter gene, we examined putative promoter elements associated with jasmonate-responsive expression of this gene. Using stably transformed plants, we first characterized the extended promoter region that positively regulates basal expression from the PDF1.2 promoter. Second, using promoter deletion constructs including one from which the GCC-box region was deleted, we observed a substantially lower response to jasmonate than lines carrying this motif. In addition, point mutations introduced into the core GCC-box sequence substantially reduced jasmonate responsiveness, whereas addition of a 20-nucleotide-long promoter element carrying the core GCC-box and flanking nucleotides provided jasmonate responsiveness to a 35S minimal promoter. Taken together, these results indicated that the GCC-box plays a key role in conferring jasmonate responsiveness to the PDF1.2 promoter. However, deletion or specific mutations introduced into the core GCC-box did not completely abolish the jasmonate responsiveness of the promoter, suggesting that the other promoter elements lying downstream from the GCC-box region may also contribute to jasmonate responsiveness. In other experiments, we identified a jasmonate- and pathogen-responsive ethylene response factor transcription factor, AtERF2, which when overexpressed in transgenic Arabidopsis plants activated transcription from the PDF1.2, Thi2.1, and PR4 (basic chitinase) genes, all of which contain a GCC-box sequence in their promoters. Our results suggest that in addition to their roles in regulating ethylene-mediated gene expression, ethylene response factors also appear to play important roles in regulating jasmonate-responsive gene expression, possibly via interaction with the GCC-box.

HMG box transcription factor gene Hbp1 is expressed in germ cells of the developing mouse testis

HMG box containing protein 1 (HBP1) is a high mobility group domain transcriptional repressor that regulates proliferation in differentiated tissues. We have found mouse Hbp1 to be expressed strongly in the embryonic mouse testis from approximately 12.5 days post coitum, compared with low levels of expression in the embryonic ovary. Expression of Hbp1 is maintained in the developing testis beyond the onset of spermatogenesis after birth. Whole-mount in situ hybridisation analysis showed that expression of Hbp1 in the XY gonad is localized within the developing testis cords, the precursors of the seminiferous tubules. Expression of Hbp1 is not apparent in testis cords of gonads from homozygous We mutant embryos, which lack germ cells. In situ hybridisation analysis on cryosectioned embryonic testis indicated that Hbp1 expression resembles that of the germ cell marker Oct4. We conclude that Hbp1 is up-regulated specifically in germ cells of the developing XY gonad. The expression of Hbp1 in XY germ cells appears to correlate with the onset of mitotic arrest in these cells. (C) 2004 Wiley-Liss, Inc.

HLS5, a novel RBCC (ring finger, B box, coiled-coil) family member isolated from a hemopoietic lineage switch, is a candidate tumor suppressor

Hemopoietic cells, apparently committed to one lineage, can be reprogrammed to display the phenotype of another lineage. The J2E erythroleukemic cell line has on rare occasions developed the features of monocytic cells. Subtractive hybridization was used in an attempt to identify genes that were up-regulated during this erythroid to myeloid transition. We report here on the isolation of hemopoietic lineage switch 5 (Hls5), a gene expressed by the monocytoid variant cells, but not the parental J2E cells. Hls5 is a novel member of the RBCC (Ring finger, B box, coiled-coil) family of genes, which includes Pml, Herf1, Tif-1alpha, and Rfp. Hls5 was expressed in a wide range of adult tissues; however, at different stages during embryogenesis, Hls5 was detected in the branchial arches, spinal cord, dorsal root ganglia, limb buds, and brain. The protein was present in cytoplasmic granules and punctate nuclear bodies. Isolation of the human cDNA and genomic DNA revealed that the gene was located on chromosome 8p21, a region implicated in numerous leukemias and solid tumors. Enforced expression of Hls5 in HeLa cells inhibited cell growth, clonogenicity, and tumorigenicity. It is conceivable that HLS5 is one of the tumor suppressor genes thought to reside at the 8p21 locus.

C/EBP delta and C/EBP gamma bind the CCAAT-box in the human beta-globin promoter and modulate the activity of the CACC-box binding protein, EKLF

Developmental- and tissue-specific expression of globin genes is mediated by a few key elements within the proximal promoter of each gene. DNA-binding assays previously identified NF-Y, GATA-1, C/EBP beta and C/EBP gamma as candidate regulators of beta-globin transcription via the CCAAT-box, a promoter element situated between CACC- and TATA-boxes. We have identified C/EBP delta as an additional beta-globin CCAAT-box binding protein. In reporter assays, we show that C/EBP delta can co-operate with EKLF, a CACC-box binding protein, to activate the beta-globin promoter, whereas C/EBP gamma inhibits the transcriptional activity of EKLF in this assay. (c) 2005 Elsevier B.V. All rights reserved.

The effect of box shape on the dynamic properties of proteins simulated under periodic boundary conditions

The effect of the box shape on the dynamic behavior of proteins simulated under periodic boundary conditions is evaluated. In particular, the influence of simulation boxes defined by the near-densest lattice packing (NDLP) in conjunction with rotational constraints is compared to that of standard box types without these constraints. Three different proteins of varying size, shape, and secondary structure content were examined in the study. The statistical significance of differences in RMSD, radius of gyration, solvent-accessible surface, number of hydrogen bonds, and secondary structure content between proteins, box types, and the application or not of rotational constraints has been assessed. Furthermore, the differences in the collective modes for each protein between different boxes and the application or not of rotational constraints have been examined. In total 105 simulations were performed, and the results compared using a three-way multivariate analysis of variance (MANOVA) for properties derived from the trajectories and a three-way univariate analysis of variance (ANOVA) for collective modes. It is shown that application of roto-translational constraints does not have a statistically significant effect on the results obtained from the different simulations. However, the choice of simulation box was found to have a small (5-10%), but statistically significant effect on the behavior of two of the three proteins included in the study. (c) 2005 Wiley Periodicals, Inc.

The Opinion Editorial: teaching physiology outside the box

Improving the public understanding of science is an important challenge for the future professional scientists who are our current undergraduates. In this paper, we present a conceptual model that explores the role of mass media as community gatekeepers of new scientific findings. This model frames the benefits for undergraduate science students to learn about media genres so that they can learn to communicate science more effectively to nonprofessional audiences. Informed by this Media Role model, we then detail a novel writing task for undergraduate physiology students, the Opinion Editorial (Op-Ed), and an accompanying Peer Review. The Op-Ed genre was directly taught to the students by a professional journalist. As an assessment task, students presented a recent, highly technical paper as an Op-Ed. This was assessed by both faculty members and peers using a detailed assessment rubric. Most students were able to replicate the features of Op-Eds and attained high grades on their writing tasks. Survey data from final-year physiology students (n = 230) were collected before and after the implementation of the Op-Ed/Peer Review. These indicated that most students were aware of the importance of scientists to effectively communicate their knowledge to nonprofessional audiences, that the Op-Ed writing task was challenging, and that they believed that their ability to write to nonprofessional audiences was improved after explicit teaching and feedback.