Multiple axon guidance cues establish the olfactory topographic map: how do these cues interact?

Each primary olfactory neuron stochastically expresses one of similar to1000 odorant receptors. The total population of these neurons therefore consists of similar to1,000 distinct subpopulations, each of which are mosaically dispersed throughout one of four semi-annular zones in the nasal cavity. The axons of these different subpopulations are initially intermingled within the olfactory nerve. However, upon reaching the olfactory bulb, they sort out and converge so that axons expressing the same odorant receptor typically target one or two glomeruli. The spatial location of each of these 1800 glomeruli are topographically-fixed in the olfactory bulb and are invariant from animal to animal. Thus, while odorant receptors are expressed mosaically by neurons throughout the olfactory neuroepithelium their axons sort out, converge and target the same glomerulus within the olfactory bulb. How is such precise and reproducible topographic targeting generated? While some of the mechanisms governing the growth cone guidance of olfactory sensory neurons are understood, the cues responsible for homing axons to their target site remain elusive.

Expression of specific glycoconjugates in both primary and secondary olfactory pathways in BALB/C mice

Binding of cell surface carbohydrates to their receptors specifically promotes axon growth and synaptogenesis in select regions of the developing nervous system. In some cases these interactions depend upon cell-cell adhesion mediated by the same glycoconjugates present on the surface of apposing cells or their processes. We have previously shown that the plant lectin Dolichos biflorus agglutinin (DBA) binds to: a subpopulation of mouse primary olfactory neurons whose axons selectively fasciculate prior to terminating in the olfactory bulb. In the present study, we investigated whether these glycoconjugates were also expressed by postsynaptic olfactory neurons specifically within the olfactory pathway. We show here for the first time that DBA ligands were expressed both by a subset of primary olfactory neurons as well as by the postsynaptic mitral/tufted cells in BALB/C mice. These glycoconjugates were first detected on mitral/tufted cell axons during the early postnatal period, at a time when there is considerable synaptogenesis and synaptic remodelling in the primary olfactory cortex. This is one of the few examples of the selective expression of molecules in contiguous axon tracts in the mammalian nervous system. These results suggest that glycoconjugates recognized by DBA may have a specific role in the formation and maintenance of neural connections within a select functional pathway in the brain. J. Comp. Neurol. 443:213-225, 2002. (C) 2002 Wiley-Liss, Inc.

Development of a measure of coping with multiple sclerosis caregiving

Development of a self-report measure of coping specific to multiple sclerosis (MS) caregiving is needed to advance our understanding of the role of coping in adaptation to caring for a person with MS and to contribute to a lack of empirical data on MS caregiving. A total of 213 MS caregivers and their care recipients completed a Coping with MS Caregiving Inventory (CMSCI) and measures of adjustment (psychological distress), appraisal and illness. A subsample (n = 64) also completed the Ways of Coping Checklist (WCC) and additional adjustment measures (depression, caregiving impact. dyadic adjustment, and relationship conflict and reciprocity). Factor analyses revealed 5 factors: Supportive Engagement, Criticism and Coercion, Practical Assistance, Avoidance, and Positive Reframing. Subscales had internal reliabilities comparable to similar scales and were empirically distinct. Preliminary construct validation data are consistent with recent MS caregiving research that links passive avoidant emotion-focused coping with poorer adjustment, and relationship-focused coping caregiving research that links greater reliance on positive relationship-focused coping and less reliance on criticism with better adjustment. Results extend this research by revealing new relations between coping and adaptation to MS caregiving. Convergent validation data suggest that although the inventory differs from the WCC, it does share certain conceptual similarities with this scale.

Paid employment of mothers and fathers of an adult child with multiple disabilities

Background Paid employment is increasingly undertaken by mothers as their children age, with the majority of women being in employment by the time their offspring are adult. Opportunities to engage in employment appear to be reduced for mothers of children with disabilities; however, little is known about the employment of mothers or fathers of adults with disabilities. Method Data were collected regarding the employment decisions of parents of a young adult with multiple disabilities and contrasted with those of parents whose children were all developing normally. Twenty-five mothers and 12 fathers of a young adult with multiple disabilities were interviewed, as were 25 comparison mothers and 19 comparison fathers. Data collected included hours of work, reasons for employment status, attitudes towards work and child care, and psychological well-being. Results Clear differences were found between the two groups. Mothers and fathers of a child with multiple disabilities showed different engagement patterns with the paid workforce from comparison parents. Hours of work for fathers of a young adult with multiple disabilities showed a bi-modal distribution, with some fathers working fewer hours than usual and others working very long hours. For mothers in both groups, the number of hours in paid employment was negatively associated with reports of psychological problems. Conclusions Increased attention needs to be given to the employment opportunities of parents of children with disabilities since employment appears to play a protective role for mothers, in particular. Services provided to adults with disabilities will need to change if parents are to have the same life chances as parents without adult offspring with a disability.

Multiple ciguatoxins present in Indian Ocean reef fish

Optimised gradient reversed-phase high-performance liquid chromatography electrospray ionisation mass spectrometry (LC/MS) methods, in combination with a [H-3]-brevetoxin binding assay (RLB), revealed multiple ciguatoxins in a partially purified extract of a highly toxic Lutjanus sebae (red emperor) from the Indian Ocean. Two major ciguatoxins of 1140.6 Da (I-CTX-1 and -2) and two minor ciguatoxins of 1156.6 Da (I-CTX-3 and -4) were identified. Accurate mass analysis revealed that I-CTX-1 and -2 and Caribbean C-CTX-1 had indistinguishable masses (1140.6316 Da, at 0.44 ppm resolution). Toxicity estimated from LC/MS/RLB responses indicated that I-CTX-1 and -2 were both similar to 60% the potency of Pacific ciguatoxin-1 (P-CTX-1). In contrast to ciguatoxins of the Pacific where the more oxidised ciguatoxins are more potent, I-CTX-3 and -4 were similar to 20% of P-CTX-1 potency. Interconversion in dilute acid or on storage, typical of spiroketal and hemiketal functionality found in P-CTXs and C-CTXs, respectively, was not observed to occur between I-CTX-1 and -2. The ratio of CTX-1 and -2 varied depending on the fish extract being analysed. These results suggest that I-CTX-1 and -2 may arise from separate dinoflagellate precursors that may be oxidatively biotransformed to I-CTX-3 and -4 in fish. (C) 2002 Published by Elsevier Science Ltd.

Factors influencing the germination of macroconidia and secondary conidia of Claviceps africana

The influences of temperature, time, and moisture on the germination of macroconidia and secondary conidia of Australian isolates of Claviceps africana were studied in vitro. The optimum temperature for germination of both macroconidia and secondary conidia of C. africana was 20degreesC. Although germination of macroconidia ceased near 31degreesC, approximately 30% of secondary conidia germinated at 37degreesC after 48 and 72 h of incubation. Sorghum flower extract agar stimulated macroconidium and secondary conidium germination, irrespective of temperature. Germination of macroconidia and secondary conidia on water agar started after 4 h of incubation at 20degreesC, reaching a maximum after 16-24 h and 14 h, respectively. Maximum germination of both macroconidia and secondary conidia was at greater than or equal to-5 bars at 20degreesC. Germination of secondary conidia ceased at -35 bars, whereas macroconidia germinated at water potentials as low as -55 bars at 20degreesC.

The triad of bilateral retinoblastoma, dysplastic naevus syndrome and multiple cutaneous malignant melanomas: a case report and review of the literature

We report a case of a patient with the triad of retinoblastoma, dysplastic naevus syndrome (DNS) and multiple cutaneous melanomas. The combination of retinoblastoma and DNS is a significant risk factor for the development of cutaneous melanoma. This risk extends to family members. We recommend that survivors of (inherited) retinoblastoma and their relatives are closely screened for the presence of dysplastic naevi. (C) 2002 Lippincott Williams Wilkins.

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 210 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The purpose of this study was to determine the pharmacokinetics of [C-14]diclofenac, [C-14]salicylate and [H-3]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. Tc-99m-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac>salicylate >clonidine>sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.

Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay

To determine which species and populations of Anopheles transmit malaria in any given situation, immunological assays for malaria sporozoite antigen can replace traditional microscopical examination of freshly dissected Anopheles. We developed a wicking assay for use with mosquitoes that identifies the presence or absence of specific peptide epitopes of circumsporozoite (CS) protein of Plasmodium falciparum and two strains of Plasmodium vivax (variants 210 and 247). The resulting assay (VecTest(TM) Malaria) is a rapid, one-step procedure using a 'dipstick' test strip capable of detecting and distinguishing between P. falciparum and P. vivax infections in mosquitoes. The objective of the present study was to test the efficacy, sensitivity, stability and field-user acceptability of this wicking dipstick assay. In collaboration with 16 test centres world-wide, we evaluated more than 40 000 units of this assay, comparing it to the standard CS ELISA. The 'VecTest(TM) Malaria' was found to show 92% sensitivity and 98.1% specificity, with 97.8% accuracy overall. In accelerated storage tests, the dipsticks remained stable for >15 weeks in dry conditions up to 45degreesC and in humid conditions up to 37degreesC. Evidently, this quick and easy dipstick test performs at an acceptable level of reliability and offers practical advantages for field workers needing to make rapid surveys of malaria vectors.

Characterisation of multiple Caribbean ciguatoxins and congeners in individual specimens of horse-eye jack (Caranx latus) by high-performance liquid chromatography/mass spectrometry

We studied the variation in toxin profiles of purified extracts of 10 individual specimens and two pools of ciguateric Caranx latus. High-performance liquid chromatography/mass spectrometry (HPLC/MS) identified in all individual samples at least seven Caribbean ciguatoxins (C-CTXs) comprising C-CTX-1 and its epimer C-CTX-2 ([M + H](+) m/z 1141.58), and five new C-CTX congeners with pseudo-molecular ions at m/z 1141.58, 1143.60, 1157.57, 1159.58, and 1127.57. In some samples, additional C-CTX isomers were detected with [M + H](+) ions at m/z 1141.58 (two), 1143.60 (one) and 1157.57 (two). The two low-toxic pools contained only four to six ciguatoxins. The comparison in relative proportions of four different mass classes ([M + H](+) at m/z 1141, 1143, 1157 and 1127) showed that the group at m/z 1157 increased (2-20%) with flesh toxicity. More than 80% of group m/z 1141 comprised C-CTX-1, C-CTX-2 and their isomer C-CTX-1 a whose level in this group correlated with fish toxicity. Contrary to low-toxic fishes, high-risk specimens had C-CTX-1 levels

Conformationally constrained macrocycles that mimic tripeptide beta-strands in water and aprotic solvents

The beta-strand conformation is unknown for short peptides in aqueous solution, yet it is a fundamental building block in proteins and the crucial recognition motif for proteolytic enzymes that enable formation and turnover of all proteins. To create a generalized scaffold as a peptidomimetic that is preorganized in a beta-strand, we individually synthesized a series of 15-22-membered macrocyclic analogues of tripeptides and analyzed their structures. Each cycle is highly constrained by two trans amide bonds and a planar aromatic ring with a short nonpeptidic linker between them. A measure of this ring strain is the restricted rotation of the component tyrosinyl aromatic ring (DeltaG(rot) 76.7 kJ mol(-1) (16-membered ring), 46.1 kJ mol(-1) (17-membered ring)) evidenced by variable temperature proton NMR spectra (DMF-d(7), 200-400 K). Unusually large amide coupling constants ((3)J(NH-CHalpha) 9-10 Hz) corresponding to large dihedral angles were detected in both protic and aprotic solvents for these macrocycles, consistent with a high degree of structure in solution. The temperature dependence of all amide NH chemical shifts (Deltadelta/T7-12 ppb/deg) precluded the presence of transannular hydrogen bonds that define alternative turn structures. Whereas similar sized conventional cyclic peptides usually exist in solution as an equilibrium mixture of multiple conformers, these macrocycles adopt a well-defined beta-strand structure even in water as revealed by 2-D NMR spectral data and by a structure calculation for the smallest (15-membered) and most constrained macrocycle. Macrocycles that are sufficiently constrained to exclusively adopt a beta-strand-mimicking structure in water may be useful pre-organized and generic templates for the design of compounds that interfere with beta-strand recognition in biology.