Mouse Sox8 is located between, not within, the t-complex deletions t(w18) and t(h20) on chromosome 17

The SOX family of developmental transcription factors is known to play critical roles in cell lineage specification, fate determination and differentiation during development in diverse phyla. Their importance is underscored by their involvement in a number of human diseases and mouse mutants, and by targeted mutation in mice. SOX8 is broadly expressed during development and is located on human chromosome 16p and within the t-complex on mouse chromosome 17, in the vicinity of two mutations t(w18) and t(h20). Here we analyse mutant genomic DNA to show that the Sox8 gene locus lies outside the deletion regions of both t(w18) and t(h20) and between these deletions. These data exclude Sox8 from contributing to the t(w18) and t(h20) phenotypes, and provide an additional marker for structural characterization of this complex genomic region. Copyright (C) 2001 S. Karger AG, Basel.

A cluster of melioidosis cases from an endemic region is clonal and is linked to the water supply using molecular typing of Burkholderia pseudomallei isolates

Nine cases of melioidosis with four deaths occurred over a 28-month period in members of a small remote Aboriginal community in the top end of the Northern Territory of Australia. Typing by pulsed-field gel electrophoresis showed isolates of Burkholderia pseudomallei from six of the cases to be clonal and also identical to an isolate from the community water supply, but not to soil isolates. The clonality of the isolates found in this cluster contrasts with the marked genetic diversity of human and environmental isolates found in this region which is hyperendemic for B. pseudomallei. It is possible that the clonal bacteria persisted and were propagated in biofilm in the water supply system. While the exact mode of transmission to humans and the reasons for cessation of the outbreak remain uncertain, contamination of the unchlorinated community water supply is a likely explanation.

The linker domain of the Ha-Ras hypervariable region regulates interactions with exchange factors, Raf-1 and phosphoinositide 3-kinase

Ha-Ras and Ki-Ras have different distributions across plasma membrane microdomains. The Ras C-terminal anchors are primarily responsible for membrane microlocalization, but recent work has shown that the interaction of Ha-Ras with lipid rafts is modulated by GTP loading via a mechanism that requires the hypervariable region (HVR). We have now identified two regions in the HVR linker domain that regulate Ha-Ras raft association. Release of activated Ha-Ras from lipid rafts is blocked by deleting amino acids 173-179 or 166-172. Alanine replacement of amino acids 173-179 but not 166-172 restores wild type micro-localization, indicating that specific N-terminal sequences of the linker domain operate in concert with a more C-terminal spacer domain to regulate Ha-Ras raft association. Mutations in the linker domain that confine activated Ha-RasG12V to lipid rafts abrogate Raf-1, phosphoinositide 3-kinase, and Akt activation and inhibit PC 12 cell differentiation. N-Myristoylation also prevents the release of activated Ha-Ras from lipid rafts and inhibits Raf-1 activation. These results demonstrate that the correct modulation of Ha-Ras lateral segregation is critical for downstream signaling. Mutations in the linker domain also suppress the dominant negative phenotype of Ha-RasS17N, indicating that HVR sequences are essential for efficient interaction of Ha-Ras with exchange factors in intact cells.

Riddling and invariance for discontinuous maps preserving Lebesgue measure

In this paper we use the mixture of topological and measure-theoretic dynamical approaches to consider riddling of invariant sets for some discontinuous maps of compact regions of the plane that preserve two-dimensional Lebesgue measure. We consider maps that are piecewise continuous and with invertible except on a closed zero measure set. We show that riddling is an invariant property that can be used to characterize invariant sets, and prove results that give a non-trivial decomposion of what we call partially riddled invariant sets into smaller invariant sets. For a particular example, a piecewise isometry that arises in signal processing (the overflow oscillation map), we present evidence that the closure of the set of trajectories that accumulate on the discontinuity is fully riddled. This supports a conjecture that there are typically an infinite number of periodic orbits for this system.

Linkage of Paget disease of bone to a novel region on human chromosome 18q23

Paget disease of bone (PDB) is characterized by increased osteoclast activity and localized abnormal bone remodeling. PDB has a significant genetic component, with evidence of linkage to chromosomes 6p21.3 (PDB1) and 18q21-22 (PDB2) in some pedigrees. There is evidence of genetic heterogeneity, with other pedigrees showing negative linkage to these regions. TNFRSF11A, a gene that is essential for osteoclast formation and that encodes receptor activator of nuclear factor-kappa B (RANK), has been mapped to the PDB2 region. TNFRSF11A mutations that segregate in pedigrees with either familial expansile osteolysis or familial PDB have been identified; however, linkage studies and mutation screening have excluded the involvement of RANK in the majority of patients with PDB. We have excluded linkage, both to PDB1 and to PDB2, in a large multigenerational pedigree with multiple family members affected by PDB. We have conducted a genomewide scan of this pedigree, followed by fine mapping and multipoint analysis in regions of interest. The peak two-point LOD scores from the genomewide scan were 2.75, at D7S507, and 1.76, at D18S70. Multipoint and haplotype analysis of markers flanking D7S507 did not support linkage to this region. Haplotype analysis of markers flanking D18S70 demonstrated a haplotype segregating with PDB in a large subpedigree. This subpedigree had a significantly lower age at diagnosis than the rest of the pedigree (51.2 +/- 8.5 vs. 64.2 +/- 9.7 years; P = .0012). Linkage analysis of this subpedigree demonstrated a peak two-point LOD score of 4.23, at marker D18S1390 (theta = 0), and a peak multipoint LOD score of 4.71, at marker D18S70. Our data are consistent with genetic heterogeneity within the pedigree and indicate that 18q23 harbors a novel susceptibility gene for PDB.

Determination of the hemispheric character (i.e. southern or northern latitudinal position) of equatorial ionosonde stations as deduced from long-term recordings of the minimum height of the F-region (h ' F)

The virtual (or minimum) height of the F-region (h'F), recorded over a number of solar cycles for I I equatorial and mid-latitude ionosonde stations, was used to deduce the hemispheric (i.e. southern or northern hemisphere) character of equatorial stations. The semi-annual median monthly height (h'F) variations consist of two components: major local summer maximum and winter sub-maximum (about 5 percent of the summer maximum). This hemispheric pattern was most consistently observed for equatorial stations (within 5degrees of the geomagnetic equator) in a period centred on the local midnight (21-03 LT) but was also present, to a lesser extent, at mid-latitude stations and at other time intervals. It is evident that the physical parameter h'F defines the hemispheric character of an equatorial station which has different (sometimes opposite) geographic and geomagnetic latitudes. There is a sharp transition in the latitudinal character of the stations on both sides of the equator leading to hypothesis that the equal maxima in h'F in December and June solstices are observed at a near-equator position labelled as ionosonde deduced equator (IDE). Such a signature was observed for an American equatorial (both geographic and geomagnetic) station Talara (Peru) which is an experimental support of the hypothesis. The IDE can be another useful parameter characterising the equatorial ionosphere. This finding reveals a new application of the standard ionosonde data in defining the geophysical character of equatorial stations, being an important contribution to space climatology. (C) 2002 Elsevier Science Ltd. All rights reserved.

Isolation of arboviruses from mosquitoes (Diptera : Culicidae) collected from the Gulf Plains region of northwest Queensland, Australia

As part of investigations into Japanese encephalitis (JE) virus and related flaviviruses in northern Australia, 153,529 mosquitoes were collected and processed for virus isolation from the Gulf Plains region of northwest Queensland. Collections front within 30 km of each of the townships of Croydon, Normanton and Karumba yielded 3,087 (2.0%), 66,009 (43.0%), and 84,433 (55.0%) mosquitoes, respectively, from which 16 viruses were isolated. Four isolates of Murray Valley encephalitis (MVE), two of Kunjin (KUN), three of Ross River (1111), and one of Sindbis (SIN) viruses were obtained from Culex sitiens subgroup mosquitoes. Molecular identification of the mosquito species composition of these virus positive pools revealed that most isolates were from pools containing mainly Culex annulirostris Skuse and low numbers of Cidex palpalis (Taylor). Only three pools, one each of MVE, KUN, and RR, were from mosquitoes identified exclusively as Cx. annulirostris. Other viruses isolated include one Edge Hill Virus from Ochlerotatus normanensis (Taylor), an isolate of SIN from Anopheles meraukensis Venhuis, two isolates of RR from Anopheles amictus Edwards, and single isolates of RR from Anopheles bancroftii Giles and Aedes lineatopennis (Ludlow). The isolate of RR from Ae. lineatopennis was the first reported from this species. The public health implications of these isolations in the Gulf Plains region are discussed briefly.

Epizootic activity of Murray Valley encephalitis virus in an aboriginal community in the southeast Kimberley region of western Australia: Results of cross-sectional and longitudinal serologic studies

Murray Valley encephalitis (MVE) virus is a mosquito-borne flavivirus causing severe encephalitis with a resultant high morbidity and mortality. In the period 1989-1993. we undertook a cross-sectional and longitudinal studs by annually screening members of a small remote Aboriginal community in northwestern Australia for MVE virus antibodies. Of the estimated 250-300 people in the community. 249 were tested, and 52.6% had positive serology to MVE. The proportion testing positive increased with increasing age group. and males were slightly more likely to be positive than females. During the study period. a high proportion of the population seroconverted to MVE: the clinical/subclinical ratio seems to be lower than previously reported. Although MVE is mostly asymptomatic, the devastating consequences of clinical illness indicate that advice should be provided regarding the avoidance of mosquito bites. Our longitudinal study showed that the risk of seroconversion was similar for each age group. not just the young.

Further observations on the Enenteridae Yamaguti, 1958 (Digenea, Lepocreadioidea) of the Indo-West Pacific region, including a new species from Western Australia

Measurements are given for all and full descriptions and illustrations for some of the following enenterid species: Enenterum aureum Linton, 1910 in Kyphosus bigibbus and K. sydneyanus? from Ningaloo Coral Reef, Western Australia, K. vaigiensis from off Heron Island, Queensland and K. vaigiensis from off Moorea, French Polynesia; E. mannarense Hafeezullah, 1980 in K. bigibbus and K. sydneyanus? from Ningaloo Coral Reef; E. elongatum Yamaguti, 1970 in K. vaigiensis from Heron Island, Queensland and K. bigibbus and K. sydneyanus? from Ningaloo Coral Reef; Koseiria alanwilliamsi sp. nov. in Kyphosus cornelii from off Kalbarri, Western Australia; Koseiria xishaense Gu et Shen, 1983 in K. vaigiensis from off Heron Island and K. bigibbus from off Palau, Micronesia; Proenenterum isocotylum Manter, 1954 in Aplodactylus arctidens from off Stanley, Tasmania; R ericotylum Manter, 1954 in A. arctidens from off Stanley; Cadenatella isuzumi Machida, 1993 from Kyphosus bigibbus and K. sydneyanus? from Ningaloo Coral Reef; Cadenatella pacifica (Yamaguti, 1970) from Kyphosus bigibbus from Ningaloo Coral Reef. Two recent cladistic studies of the Enenteridae are discussed and a further analysis has shown that Enenterum and Cadenatella are monophyletic, whilst Koseiria appears polyphyletic. The zoogeography and host-specificity of Kyphosus-inhabiting enenterids is discussed.

New graptolite faunas from the Llandovery, lower Silurian of the Graveyard Creek Subprovince, Broken River region, Queensland, Australia

A continuous biostratigraphic sequence has been established, possibly from as low as the sedgwickii Biozone but certainly throughout the Telychian Stage (?sedgwickii, turriculatus, ?crispus, griestoniensis and crenulata biozones). Thirty-three taxa have been recorded, including the new genus Wandograptus wandovalensis sp. nov., the new species Pseudostreptograptus queenslandensis and the new subspecies Dictyonema paululum australis and Stimulograptus sedwickii loydelli. A number of species have been recorded from Australia for the first time: Dictyonema cf. geniculatum Bulman, Petalolithus kurcki (Rickards), Pristiograptus initialis (Kirste), Monoclimacis directa Zalasciewicz, Monograptus aff. distans (Portlock), Monograptus sartorius Törnquist, and Torquigraptus pragensis (Bouček). Nine forms have been left under open nomenclature. The type section for the Poley Cow Formation yields a griestoniensis biozone fauna close to the top, and this level can be correlated with a griestoniensis Biozone fauna in the Broken River crossing section, again just below the top of the formation. Further north, griestoniensis Biozone faunas have also been recognized, beyond Diggers Creek, and in the Quinton Formation at Top Hut, enabling a reliable time plane throughout the region. At Top Hut, the highest graptolitic strata yield a crenulata Biozone fauna; and stratigraphically lower sequences, referable to the ?sedgwickii, turriculatus and ?crispus biozones, have been established on the Broken River section. It is likely that a full Telychian (Upper Llandovery) sequence occurs in the Poley Cow and Quinton formations enabling accurate correlation with other parts of the world.

A lipid core peptide construct containing a conserved region determinant of the group a streptococcal M protein elicits heterologous opsonic antibodies

The study reported here investigated the immunogenicity and protective potential of a lipid core peptide (LCP) construct containing a conserved region determinant of M protein, defined as peptide J8. Parenteral immunization of mice with LCP-J8 led to the induction of high-titer serum immunoglobulin G J18-specific antibodies when the construct was coadministered with complete Freund's adjuvant (CFA) or administered alone. LCP-J8 in CFA had significantly enhanced immunogenicity compared with the monomeric peptide J8 given in CFA. Moreover, LCP-J8/CFA and LCP-J8 antisera opsonized four different group A streptococcal (GAS) strains, and the antisera did not cross-react with human heart tissue proteins. These data indicate the potential of an LCP-based M protein conserved region GAS vaccine in the induction of broadly protective immune responses in the absence of a conventional adjuvant.

Single-chain antibodies produced by phage display against the C-terminal 19 kDa region of merozoite surface protein-1of Plasinodium yoelii reduce parasite growth following challenge

Antibodies have the potential to be therapeutic reagents for malaria. Here we describe the production of a novel phage antibody display library against the C-terminal 19 kDa region of the Plasmodium yoelii YM merozoite surface protein-1 (MSP1(19)). In vivo studies against homologous lethal malaria challenge show an anti-parasite effect in a dose dependent manner, and analysis by plasmon resonance indicates binding to the antigen is comparable to the binding of a protective monoclonal antibody. The data support the lack of a need for any antibody Fc-related function and hold great significance for the development of a therapeutic reagent for malaria. (C) 2002 Elsevier Science Ltd. All rights reserved.

Load-unload response ratio and accelerating moment/energy release critical region scaling and earthquake prediction

The main idea of the Load-Unload Response Ratio (LURR) is that when a system is stable, its response to loading corresponds to its response to unloading, whereas when the system is approaching an unstable state, the response to loading and unloading becomes quite different. High LURR values and observations of Accelerating Moment/Energy Release (AMR/AER) prior to large earthquakes have led different research groups to suggest intermediate-term earthquake prediction is possible and imply that the LURR and AMR/AER observations may have a similar physical origin. To study this possibility, we conducted a retrospective examination of several Australian and Chinese earthquakes with magnitudes ranging from 5.0 to 7.9, including Australia's deadly Newcastle earthquake and the devastating Tangshan earthquake. Both LURR values and best-fit power-law time-to-failure functions were computed using data within a range of distances from the epicenter. Like the best-fit power-law fits in AMR/AER, the LURR value was optimal using data within a certain epicentral distance implying a critical region for LURR. Furthermore, LURR critical region size scales with mainshock magnitude and is similar to the AMR/AER critical region size. These results suggest a common physical origin for both the AMR/AER and LURR observations. Further research may provide clues that yield an understanding of this mechanism and help lead to a solid foundation for intermediate-term earthquake prediction.