Familial partial epilepsy with variable foci: A new partial epilepsy syndrome with suggestion of linkage to chromosome 2

Familial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75-43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome-wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.

Critical values for unit root and cointegration test statistics - the use of response surface equations

This note considers the value of surface response equations which can be used to calculate critical values for a range of unit root and cointegration tests popular in applied economic research.

STD syndrome packets: Improving syndromic management of sexually transmitted diseases in developing countries

Objective: To design, introduce, and evaluate STD syndrome packets containing recommended drugs for each syndrome, four condoms, a partner treatment card, and a patient information leaflet, with the goal of improving sexually transmitted disease (STD) case management. Methods: Packet design evolved around available packaging technology, informed by pilot testing with nurses working in primary care clinics, doctors in private medical practices, and patients with an STD, in Hlabisa, South Africa. Evaluation 1 year later included analysis of distribution records and interviews with 16 nurses and 61 patients. Results: A cheap packet (2 U, S, cents each, excluding contents) compatible with current legislation was designed and introduced to six public sector clinics and as a short pilot to five private medical practices, Four thousand eighty-five packets were distributed to the clinics, equivalent to approximately 115% of the STDs reported over that period. All 16 nurses reported using the packets, but only 63% did so all the time because of occasional supply problems, All believed the packets improved treatment by saving time (75%), improving supply of condoms and partner cards (44%), and making treatment easier (56%), Patients also responded positively, and most said they would buy a packet (up to $5) at a pharmacy (84%) or store (63%) if available. Conclusions: The STD syndrome packets have the potential to improve STD syndromic management by standardizing therapy and improving the supply of condoms, partner cards, and information leaflets. Packets are popular with practitioners and patients, but consistent supply is essential for maximal impact, There may be scope for social marketing of the packets, which could further increase use.

The novel mitochondrial gene arrangement of the cattle tick, Boophilus microplus: Fivefold tandem repetition of a coding region

We sequenced across all of the gene boundaries in the mitochondrial genome of the cattle tick, Boophilus microplus, to determine the arrangement of its genes. The mtDNA of B. microplus has a coding region, composed of tRNA(Glu) and 60 bp of the 3' end of ND1, that is repeated five times. Boophilus microplus is the first coelomate animal known to have more than two copies of a coding sequence. The mitochondrial genome of B, microplus has other unusual features, including (1) reduced T arms in tRNAs, (2) an AT bias in codon use, (3) two control regions that have evolved in concert, (4) three gene rearrangements, and (5) a stem-loop between tRNA(Gln) and tRNA(Phe). The short T arms and small control regions (CRs) of B. microplus and other ticks suggest strong selection for small genomes. Imprecise termination of replication beyond its origin, which can account for the evolution of tandem repeats of coding regions in other mitochondrial genomes, cannot explain the evolution of the fivefold repeated sequence in the mitochondrial genome of B. microplus. Instead, slipped-strand mispairing or recombination are the most plausible explanations for the evolution of these tandem repeats.

Phase diagram for a class of spin-1/2 Heisenberg models interpolating between the square-lattice, the triangular-lattice, and the linear-chain limits

We study the spin-1/2 Heisenberg models on an anisotropic two-dimensional lattice which interpolates between the square lattice at one end, a set of decoupled spin chains on the other end, and the triangular-lattice Heisenberg model in between. By series expansions around two different dimer ground states and around various commensurate and incommensurate magnetically ordered states, we establish the phase diagram for this model of a frustrated antiferromagnet. We find a particularly rich phase diagram due to the interplay of magnetic frustration, quantum fluctuations, and varying dimensionality. There is a large region of the usual two-sublattice Neel phase, a three-sublattice phase for the triangular-lattice model, a region of incommensurate magnetic order around the triangular-lattice model, and regions in parameter space where there is no magnetic order. We find that the incommensurate ordering wave vector is in general altered from its classical value by quantum fluctuations. The regime of weakly coupled chains is particularly interesting and appears to be nearly critical. [S0163-1829(99)10421-1].

Brain region-specific studies of the excitatory behavioral effects of morphine-3-glucuronide

This study was designed to determine in rats whether morphine-3-glucuronide (M3G) produces its neuro-excitatory effects most potently in the ventral hippocampus (as has been reported previously for subanalgesic doses of opioid peptides). Guide cannulae were implanted into one of seven regions of the rat brain: lateral ventricle; ventral, CA1 and CA2-CA3 regions of the hippocampus; amygdala; striatum or cortex. After a 7 day recovery period, rats received intracerebral injections of (i) M3G (1.1 or 11 nmol) (ii) DADLE ([D-Ala(2),D-Leu(5)]enkephalin), (45 nmol, positive controls) or (iii) vehicle (deionised water), and behavioral excitation was quantified over 80 min. High-dose M3G (11 nmol) evoked behavioral excitation in all brain regions but the onset, severity and duration of these effects varied considerably among brain regions. By contrast, low-dose M3G (1.1 nmol) evoked excitatory behaviors only when administered into the ventral hippocampus and the amygdala, with the most potent effects being observed in the ventral hippocampus. Prior administration of the nonselective opioid antagonists, naloxone and beta-funaltrexamine into the ventral hippocampus, markedly attenuated low-dose M3G's excitatory effects but did not significantly alter levels of excitation evoked by high-dose M3G. Naloxone given 10 min after M3G (1.1 or 11 nmol) did not significantly attenuate behavioral excitation. Thus, M3G's excitatory behavioral effects occur most potently in the ventral hippocampus as reported previously for subanalgesic doses of opioid peptides, and appear to be mediated through at least two mechanisms, one possibly involving excitatory opioid receptors and the other, non-opioid receptors.

V4 region of small subunit rDNA indicates polyphyly of the Fellodistomidae (Digenea) which is supported by morphology and life-cycle data

There is no morphological synapomorphy for the disparate digeneans, the Fellodistomidae Nicoll, 1909. Although all known life-cycles of the group include bivalves as first intermediate hosts, there is no convincing morphological synapomorphy that can be used to unite the group. Sequences from the V4 region of small subunit (18S) rRNA genes were used to infer phylogenetic relationships among 13 species of Fellodistomidae from four subfamilies and eight species from seven other digenean families: Bivesiculidae; Brachylaimidae; Bucephalidae; Gorgoderidae; Gymnophallidae; Opecoelidae; and Zoogonidae. Outgroup comparison was made initially with an aspidogastrean. Various species from the other digenean families were used as outgroups in subsequent analyses. Three methods of analysis indicated polyphyly of the Fellodistomidae and at least two independent radiations of the subfamilies, such that they were more closely associated with other digeneans than to each other. The Tandanicolinae was monophyletic (100% bootstrap support) and was weakly associated with the Gymnophallidae (< 50-55% bootstrap support). Monophyly of the Baccigerinae was supported with 78-87% bootstrap support, and monophyly of the Zoogonidae + Baccigerinae received 77-86% support. The remaining fellodistomid species, Fellodistomum fellis, F. agnotum and Coomera brayi (Fellodistominae) plus Proctoeces maculatus and Complexobursa sp. (Proctoecinae), formed a separate clade with 74-92% bootstrap support. On the basis of molecular, morphological and life-cycle evidence, the subfamilies Baccigerinae and Tandanicolinae are removed from the Fellodistomidae and promoted to familial status. The Baccigerinae is promoted under the senior synonym Faustulidae Poche, 1926, and the Echinobrevicecinae Dronen, Blend & McEachran, 1994 is synonymised with the Faustulidae. Consequently, species that were formerly in the Fellodistomidae are now distributed in three families: Fellodistomidae; Faustulidae (syn. Baccigerinae Yamaguti, 1954); and Tandanicolidae Johnston, 1927. We infer that the use of bivalves as intermediate hosts by this broad range of families indicates multiple host-switching events within the radiation of the Digenea.

Phylogeographic differentiation in the mitochondrial control region in the koala, Phascolarctos cinereus (Goldfuss 1817)

The koala, Phascolarctos cinereus, is a geographically widespread species endemic to Australia, with three currently recognized subspecies: P.c. adustus, P.c. cinereus, and P.c. victor. Intraspecific variation in the mitochondrial DNA (mtDNA) control region was examined in over 200 animals from 16 representative populations throughout the species' range. Eighteen different haplotypes were defined in the approximate to 860 bp mtDNA control region as determined by heteroduplex analysis/temperature gradient gel electrophoresis (HDA/TGGE). Any single population typically possessed only one or two haplotypes yielding an average within-population haplotypic diversity of 0.180 +/- 0.003, and nucleotide diversity of 0.16%. Overall, mtDNA control region sequence diversity between populations averaged 0.67%, and ranged from 0% to 1.56%. Nucleotide divergence between populations averaged 0.51%, and ranged from 0% to 1.53%. Neighbour-joining methods revealed limited phylogenetic distinction between geographically distant populations of koalas, and tentative support for a single evolutionarily significant unit (ESU). This is consistent with previous suggestions that the morphological differences formalized by subspecific taxonomy may be interpreted as clinal variation. Significant differentiation in mtDNA-haplotype frequencies between localities suggested that little gene now currently exists among populations. When combined with microsatellite analysis, which has revealed substantial differentiation among koala populations, we conclude that the appropriate short-term management unit (MU) for koalas is the local population.

Changing patterns of coronary heart disease in the hunter region of New South Wales, Australia

A population-based observational study of men acid women aged 35-69 years in the Hunter Region of New South Wales, Australia, was conducted to assess the impact. of risk-factor modification and increased drug therapy on the trends in major coronary events and case fatality. From 1985 to 1993, there were 3006 coronary deaths and 6450 nonfatal major coronary events. Rates of death and nonfatal myocardial infarction declined, but there was an increase in hospital admissions for prolonged chess pain. Reductions in cigarette smoking, diastolic blood pressure, total cholesterol, and increased use of aspirin can fully explain the 3.3% (95% confidence interval [CI] 2.4, 4.2) average annual reduction in rates of major coronary events for men and the 4.1% (95% CI 2.7, 5.5) reduction for women. In contrast, increased use of aspirin, beta-blockers, fibrinolytic therapy, and angiotensin-converting enzyme inhibitors explain less than hall of the 8.9% (95% CI 5.9, 11.8) and 6.9% (95% CI 2.7, 10.9) average annual reduction in case fatality in hospital for men and women, respectively. These trends suggest a decline in severity of coronary heart disease consistent with reductions in risk-factor levels and improved acute medical treatment. J CLIN EPIDEMIOL 52;8:761-771, 1999. (C) 1999 Elsevier Science Inc.

Paramagnetic limiting of the upper critical field of the layered organic superconductor kappa-(BEDT-TTF)(2)Cu(SCN)(2)

We report detailed measurements of the interlayer magnetoresistance of the layered organic superconductor kappa-(BEDT-TTF)(2)Cu(SCN)(2) for temperatures down to 0.5 K and fields up to 30 T. The upper critical field is determined from the resistive transition for a wide range of temperatures and field directions. For magnetic fields parallel to the layers, the upper critical field increases approximately linearly with decreasing temperature. The upper critical field at low temperatures is compared to the Pauli paramagnetic limit, at which singlet superconductivity should be destroyed by the Zeeman splitting of the electron spins. The measured value is comparable to a value for the paramagnetic limit calculated from thermodynamic quantities but exceeds the limit calculated from BCS theory. The angular dependence of the upper critical field shows a cusplike feature for fields close to the layers, consistent with decoupled layers.

Overview, critical assessment, and conservation implications of koala distribution and abundance

Regional and national surveys provide a broadscale description of the koala's present distribution in Australia. A detailed understanding of its distribution is precluded, however, by past and continuing land clearing across large parts of the koala's range. Koala population density increased in some regions during the late 1800s and then declined dramatically in the early 1900s. The decline was associated with habitat loss, hunting, disease, fire, and drought. Declines are continuing in Queensland and New South Wales. In contrast, dense koala populations in habitat isolates in Victoria and South Australia are managed to reduce population size and browse damage. Current understanding of koala distribution and abundance suggests that the species does not meet Australian criteria as endangered or vulnerable fauna. Its conservation status needs to be reviewed, however, in light of the extensive land clearing in New South Wales and Queensland since the last (1980s) broadscale surveys. Consequently, we recommend that broadacre clearing by curtailed in New South Wales and Queensland and that regular, comprehensive, standardized, national koala surveys be undertaken. Given the fragmentation of koala habitat and regional differences in the status of the koala, we recommended that studies on regional variation in the koala be intensified and that koala ecology in fragmented and naturally restricted habitats be developed. More generally, the National Koala Conservation Strategy should be implemented.

Acyclic permutants of naturally occurring cyclic proteins - Characterization of cystine knot and beta-sheet formation in the macrocyclic polypeptide kalata B1

Kalata B1 is a prototypic member of the unique cyclotide family of macrocyclic polypeptides in which the major structural features are a circular peptide backbone, a triple stranded beta-sheet, and a cystine knot arrangement of three disulfide bonds. The cyclotides are the only naturally occurring family of circular proteins and have prompted us to explore the concept of acyclic permutation, i.e. opening the backbone of a cross-linked circular protein in topologically permuted ways. We have synthesized the complete suite of acyclic permutants of kalata B1 and examined the effect of acyclic permutation on structure and activity. Only two of six topologically distinct backbone loops are critical for folding into the native conformation, and these involve disruption of the embedded ring in the cystine knot. Surprisingly, it is possible to disrupt regions of the p-sheet and still allow folding into native-like structure, provided the cystine knot is intact. Kalata B1 has mild hemolytic activity, but despite the overall structure of the native peptide being retained in all but two cases, none of the acyclic permutants displayed hemolytic activity. This loss of activity is not localized to one particular region and suggests that cyclization is critical for hemolytic activity.

Functional implications of the human T-lymphotropic virus type 1 transmembrane glycoprotein helical hairpin structure

Retrovirus entry into cells follows receptor binding by the surface exposed envelope glycoprotein (Env) subunit (SU), which triggers the membrane fusion activity of the transmembrane (TM) protein. TM protein fragments expressed in the absence of SU adopt helical hairpin structures comprising a central coiled coil, a region of chain reversal containing a disulfide-bonded loop, and a C-terminal segment that packs onto the exterior of the coiled coil in an antiparallel manner. Here we used in vitro mutagenesis to test the functional role of structural elements observed in a model helical hairpin, gp21 of human T-lymphotropic virus type 1. Membrane fusion activity requires the stabilization of the N and C termini of the central coiled coil by a hydrophobic N cap and a small hydrophobic core, respectively. A conserved Gly-Gly hinge motif preceding the disulfide-bonded loop, a salt bridge that stabilizes the chain reversal region, and interactions between the C-terminal segment and the coiled coil are also critical for fusion activity. Our data support a model whereby the chain reversal region transmits a conformational signal from receptor-bound SU to induce the fusion-activated helical hairpin conformation of the TM protein.