Comparability of perceptual analysis of speech characteristics in Australian and Swedish speakers with multiple sclerosis

The aims of the present study were to compare the perceptual assessments of deviant speech signs (dysarthria) exhibited by Australian and Swedish speakers with multiple sclerosis (MS) and to explore whether judgements of dysarthria differed depending on whether the speakers and the judges spoke the same or different languages. Ten Australian and 10 Swedish individuals with MS (matched as closely as possible for age, gender, progression type and severity of dysarthria) were assessed by 2 Australian and 2 Swedish clinically experienced judges using a protocol including 33 speech parameters. Results show that the following perceptual dimensions were identified by both pairs of judges in both groups of speakers to a just noticeable or moderate degree: imprecise consonants, inappropriate pitch level, reduced general rate, and glottal fry. The reliability (Spearman rank-order correlation) of the consensus ratings from the Australian and the Swedish judges was high, with a mean rho of 85.7 for the Australian speakers and mean rho of 84.3 for the Swedish speakers. The most difficult perceptual parameters to assess (i.e. to agree on) included harshness, level of pitch and loudness, precision of consonants and general stress pattern. The study indicated that perceptual assessments of speech characteristics in individuals with MS are informative and can be achieved with high inter-judge reliability irrespective of the judge's knowledge of the speaker's language. Copyright (C) 2003 S. Karger AG, Basel.

Genetic analysis of complex demographic scenarios: Spatially expanding populations of the cane toad, Bufo marinus

Inferring the spatial expansion dynamics of invading species from molecular data is notoriously difficult due to the complexity of the processes involved. For these demographic scenarios, genetic data obtained from highly variable markers may be profitably combined with specific sampling schemes and information from other sources using a Bayesian approach. The geographic range of the introduced toad Bufo marinus is still expanding in eastern and northern Australia, in each case from isolates established around 1960. A large amount of demographic and historical information is available on both expansion areas. In each area, samples were collected along a transect representing populations of different ages and genotyped at 10 microsatellite loci. Five demographic models of expansion, differing in the dispersal pattern for migrants and founders and in the number of founders, were considered. Because the demographic history is complex, we used an approximate Bayesian method, based on a rejection-regression algorithm. to formally test the relative likelihoods of the five models of expansion and to infer demographic parameters. A stepwise migration-foundation model with founder events was statistically better supported than other four models in both expansion areas. Posterior distributions supported different dynamics of expansion in the studied areas. Populations in the eastern expansion area have a lower stable effective population size and have been founded by a smaller number of individuals than those in the northern expansion area. Once demographically stabilized, populations exchange a substantial number of effective migrants per generation in both expansion areas, and such exchanges are larger in northern than in eastern Australia. The effective number of migrants appears to be considerably lower than that of founders in both expansion areas. We found our inferences to be relatively robust to various assumptions on marker. demographic, and historical features. The method presented here is the only robust, model-based method available so far, which allows inferring complex population dynamics over a short time scale. It also provides the basis for investigating the interplay between population dynamics, drift, and selection in invasive species.

In vitro and in silico analysis of signal peptides from the human blood fluke, Schistosoma mansoni

Proteins secreted by and anchored on the surfaces of parasites are in intimate contact with host tissues. The transcriptome of infective cercariae of the blood fluke, Schistosoma mansoni, was screened using signal sequence trap to isolate cDNAs encoding predicted proteins with an N-terminal signal peptide. Twenty cDNA fragments were identified, most of which contained predicted signal peptides or transmembrane regions, including a novel putative seven-transmembrane receptor and a membrane-associated mitogen-activated protein kinase. The developmental expression pattern within different life-cycle stages ranged from ubiquitous to a transcript that was highly upregulated in the cercaria. A bioinformatics-based comparison of 100 signal peptides from each of schistosomes, humans, a parasitic nematode and Escherichia coli showed that differences in the sequence composition of signal peptides, notably the residues flanking the predicted cleavage site, might account for the negative bias exhibited in the processing of schistosome signal peptides in mammalian cells. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

An experimental and finite element poroelastic creep response analysis of an intervertebral hydrogel disc model in axial compression

A hydrogel intervertebral disc (lVD) model consisting of an inner nucleus core and an outer anulus ring was manufactured from 30 and 35% by weight Poly(vinyl alcohol) hydrogel (PVA-H) concentrations and subjected to axial compression in between saturated porous endplates at 200 N for 11 h, 30 min. Repeat experiments (n = 4) on different samples (N = 2) show good reproducibility of fluid loss and axial deformation. An axisymmetric nonlinear poroelastic finite element model with variable permeability was developed using commercial finite element software to compare axial deformation and predicted fluid loss with experimental data. The FE predictions indicate differential fluid loss similar to that of biological IVDs, with the nucleus losing more water than the anulus, and there is overall good agreement between experimental and finite element predicted fluid loss. The stress distribution pattern indicates important similarities with the biological lVD that includes stress transference from the nucleus to the anulus upon sustained loading and renders it suitable as a model that can be used in future studies to better understand the role of fluid and stress in biological IVDs. (C) 2005 Springer Science + Business Media, Inc.

Fractal analysis of pyramidal cells in the visual cortex of the galago (Otolemur garnetti): Regional variation in dendritic branching patterns between visual areas

Previously it has been shown that the branching pattern of pyramidal cells varies markedly between different cortical areas in simian primates. These differences are thought to influence the functional complexity of the cells. In particular, there is a progressive increase in the fractal dimension of pyramidal cells with anterior progression through cortical areas in the occipitotemporal (OT) visual stream, including the primary visual area (V1), the second visual area (V2), the dorsolateral area (DL, corresponding to the fourth visual area) and inferotemporal cortex (IT). However, there are as yet no data on the fractal dimension of these neurons in prosimian primates. Here we focused on the nocturnal prosimian galago (Otolemur garnetti). The fractal dimension (D), and aspect ratio (a measure of branching symmetry), was determined for I I I layer III pyramidal cells in V1, V2, DL and IT. We found, as in simian primates, that the fractal dimension of neurons increased with anterior progression from V1 through V2, DL, and IT. Two important conclusions can be drawn from these results: (1) the trend for increasing branching complexity with anterior progression through OT areas was likely to be present in a common primate ancestor, and (2) specialization in neuron structure more likely facilitates object recognition than spectral processing.

Parental occupation and Ewing's sarcoma: Pooled and meta-analysis

Etiologic data on Ewing's sarcoma family of tumors (ESFT) are limited, with only 5 case-control studies reported. Interesting associations, particularly related to parental occupation, have been noted, but results are somewhat inconsistent. We conducted a pooled analysis of 3 case-control studies to assess the overall associations between parental occupation and ESFT. The pooled analysis provided data on parental occupational exposure on 199 cases of ESFT and 1,451 controls. The pooled odds ratio for the periconception and gestation periods were 2.3 (95% CI = 1.3-4.1) for children whose fathers had worked on farms and 3.9 (95% CI 1.6-9.9) for those whose mothers had farmed. For the periconception and gestation periods, there was a 3.5-fold increased risk for those with both parents having farmed and a doubling of risk for those with at least one parent having farmed; pattern of increasing risk with increasing number of years of postnatal parental exposure to farms was seen. No other occupational group (or more narrowly defined occupations) had other than minor inconsistent associations with the occurrence of ESFT. In addition, we conducted a meta-analysis of farm occupation (a main risk factor) including all 4 case-control studies that collected required information to consider parental occupation. Results of the meta-analysis were consistent with those from the pooled analysis. This collaborative analysis of available individual data on parental occupation and ESFT in the offspring provides evidence supporting the hypothesis of an association between ESFT and parental occupation in farming. © 2005 Wiley-Liss, Inc.

Analysis of articulatory dynamics in dysarthria following brain injury in childhood using electromagnetic articulography and electropalatography

Two physiological assessments, electromagnetic articulography (EMA) and electropalatography (EPG), were used simultaneously to investigate the articulatory dynamics in an 18-year-old male with dysarthria 9 years following traumatic brain injury (TBI). Eight words consisting of /t, s, integral, k/ in word initial and word final positions were produced up to 10 times. A nonneurologically impaired male served as a control subject. Six parameters were analyzed using EMA: velocity, acceleration, deceleration, distance, duration, and motion path of tongue movements. Using EPG, the pattern and amount of tongue-to-palate contact and the duration of the closure/constriction phase of each consonant produced were assessed. Timing disturbances in the TBI speaker's speech were highlighted in perceptual assessments in the form of prolonged phonemes and a reduced speech rate. EMA analysis revealed that the approach and release phase durations of the consonant productions were within normal limits. Kinematic strategies such as decreased velocity and decreased distances traveled by the tongue, however, may have counterbalanced each other to produce these appropriate results. EPG examination revealed significantly longer closure/constriction phase periods, which may have contributed to the prolonged phonemes and reduced speech rate observed. The implications of these findings for the development of treatment programs for dysarthria subsequent to TBI will be highlighted.

Analysis of distinct tartrate-resistant acid phosphatase promoter regions in transgenic mice

The tartrate-resistant acid phosphatase (TRAP) is present in multiple tissues, including kidney, liver, lung, spleen, and bone. Recent study of (TRAP) gene expression has provided evidence for distinct promoters within the (TRAP) gene, suggesting that the gene has alternative, tissue-preferred mRNA transcripts. Examination of endogenous (TRAP) exon 1B and 1C mRNA transcripts revealed tissue-preferred transcript abundance with increased exon 1B transcripts detected in liver and kidney and increased exon 1C transcripts detected in bone and spleen. In this investigation, we have made transgenic mice that express a marker gene driven by two candidate promoters, designated BC and C, within the (TRAP) gene. The BC and C promoters are 2.2 and 1.6 kb, respectively, measured from the translation initiation site. Evaluation of BC transgenic lines demonstrated robust expression in multiple tissues. In contrast, significant transgene expression was not detected in C transgenic lines. Evaluation of transgene mRNAs in BC transgenic lines revealed that virtually all expression was in the form of B transcripts, suggesting that the tissue-preferred pattern of endogenous (TRAP) was not replicated in the BC transgenic line. Likewise, osteoclastogenic cultures from BC, but not C, transgenic bone marrow cells expressed the transgene following receptor activator of NFkappaB ligand/macrophage colony-stimulating factor stimulation. In conclusion, when compared with the 2.2-kb BC portion of the (TRAP) promoter region, the 1.6-kb C portion does not account for significant gene expression in vivo or in vitro; production of the bone- and spleen-preferred (TRAP) C transcript must depend on regulatory elements outside of the 2.2-kb promoter. As the majority of currently investigated transcription factors that influence transcriptional regulation of osteoclast gene expression bind within the 1.6-kb C portion of the (TRAP) promoter, it is likely that transcription binding sites outside of the 2.2-kb region will have profound effects on regulation of the gene in vivo and in vitro.

Analysis of O-glycosylation site occupancy in bovine kappa-casein glycoforms separated by two-dimensional gel electrophoresis

The ability of two-dimensional gel electrophoresis (2-DE) to separate glycoproteins was exploited to separate distinct glycoforms of kappa-casein that differed only in the number of O-glycans that were attached. To determine where the glycans were attached, the individual glycoforms were digested in-gel with pepsin and the released glycopeptides were identified from characteristic sugar ions in the tandem mass spectrometry (MS) spectra. The O-glycosylation sites were identified by tandem MS after replacement of the glycans with ammonia/aminoethanethiol. The results showed that glycans were not randomly distributed among the five potential glycosylation sites in kappa-casein. Rather, glycosylation of the monoglycoform could only be detected at a single site, T-152. Similarly the diglycoform appeared to be modified exclusively at T-152 and T-163, while the triglycoform was modified at T-152, T-163 and T-154. While low levels of glycosylation at other sites cannot be excluded the hierarchy of site occupation between glycoforms was clearly evident and argues for an ordered addition of glycans to the protein. Since all five potential O-glycosylation sites can be glycosylated in vivo, it would appear that certain sites remain latent until other sites are occupied. The determination of glycosylation site occupancy in individual glycoforms separated by 2-DE revealed a distinct pattern of in vivo glycosylation that has not been recognized previously.

The applicability of recurrent neural networks for biological sequence analysis

Selection of machine learning techniques requires a certain sensitivity to the requirements of the problem. In particular, the problem can be made more tractable by deliberately using algorithms that are biased toward solutions of the requisite kind. In this paper, we argue that recurrent neural networks have a natural bias toward a problem domain of which biological sequence analysis tasks are a subset. We use experiments with synthetic data to illustrate this bias. We then demonstrate that this bias can be exploitable using a data set of protein sequences containing several classes of subcellular localization targeting peptides. The results show that, compared with feed forward, recurrent neural networks will generally perform better on sequence analysis tasks. Furthermore, as the patterns within the sequence become more ambiguous, the choice of specific recurrent architecture becomes more critical.

A genome scan for epidermal skin pattern in adolescent twins reveals suggestive linkage on 12p13.31

Deterioration in stratum corneum reticular patterning (skin pattern or skin wrinkling) has been associated with increased rates of solar keratoses and skin cancer. A previous analysis of data from the twin sample used in this investigation has shown that 86% of the variation in skin pattern is genetic at age 12 and 62% in an adult sample (mean age 47.5). Variation due to genetic influences is likely to be influenced by more than one locus. Here, we present results of a genome-wide linkage scan of skin pattern in adolescent twins and siblings from 428 nuclear twin families. Sib-pair linkage analysis was performed on skin pattern data collected from twins at age 12 (378 informative families) and 14 (316 families). Suggestive linkage was found at marker D12S397 (12p13.31, logarithm of the odds (lod) 1.94), when the effect of the trait locus was modelled to influence the skin pattern equally at both ages 12 and 14. In the same analysis, a peak was seen at 4q23 with a lod score of 1.55. A possible candidate for the peak at 12p13.31 is the protease inhibitor, alpha-2-macroglobulin.

A need for caution in the use of frontal analysis continuous capillary electrophoresis for the determination of ligand binding data

Attention is drawn to a need for caution in the determination of binding data for protein-polyelectrolyte interactions by frontal analysis continuous capillary electrophoresis (FACCE). Because the method is valid only for systems involving comigration of complex(es) and slower-migrating reactant, establishing conformity with that condition is clearly a prerequisite for its application. However, that requirement has not been tested in any published studies thus far. On the basis of calculated FACCE patterns, presented to illustrate features by which such comigration of complex(es) and slower-migrating reactant can be identified, the form of the published pattern for a P-lactoglobulin-poly(styrenesulfonate) mixture does not seem to signify the migration behavior required to justify its consideration in such terms. Additional experimental studies are therefore needed to ascertain the validity of FACCE as a means of determining binding data for the characterization of protein-polyelectrolyte interactions. (c) 2005 Elsevier Inc. All rights reserved.

Characterizing a tropical deforestation wave: a dynamic spatial analysis of a deforestation hotspot in the Colombian Amazon

Tropical deforestation is the major contemporary threat to global biodiversity, because a diminishing extent of tropical forests supports the majority of the Earth's biodiversity. Forest clearing is often spatially concentrated in regions where human land use pressures, either planned or unplanned, increase the likelihood of deforestation. However, it is not a random process, but often moves in waves originating from settled areas. We investigate the spatial dynamics of land cover change in a tropical deforestation hotspot in the Colombian Amazon. We apply a forest cover zoning approach which permitted: calculation of colonization speed; comparative spatial analysis of patterns of deforestation and regeneration; analysis of spatial patterns of mature and recently regenerated forests; and the identification of local-level hotspots experiencing the fastest deforestation or regeneration. The colonization frontline moved at an average of 0.84 km yr(-1) from 1989 to 2002, resulting in the clearing of 3400 ha yr(-1) of forests beyond the 90% forest cover line. The dynamics of forest clearing varied across the colonization front according to the amount of forest in the landscape, but was spatially concentrated in well-defined 'local hotspots' of deforestation and forest regeneration. Behind the deforestation front, the transformed landscape mosaic is composed of cropping and grazing lands interspersed with mature forest fragments and patches of recently regenerated forests. We discuss the implications of the patterns of forest loss and fragmentation for biodiversity conservation within a framework of dynamic conservation planning.

How is leflunomide prescribed and used in Australia? analysis of prescribing and adverse effect reporting

Purpose To evaluate the use of leflunomide in the Australian community since introduction in 2000. Trends in adverse drug reaction (ADR) reporting were also studied. Methods Annual Australian prescription and dispensing statistics were analysed. Drug utilisation was estimated as defined daily doses (DDD)/1000 inhabitants/day. ADR data from the Therapeutic Goods Administration's Adverse Drug Reactions Advisory Committee (ADRAC) national monitoring system were compared with the World Health Organisation (WHO) Vigibase records. Results Leflunomide use in Australia (dispensing data) increased from 0.2 in 2000 to 0.4 DDD/1000 inhabitants/day in 2002. The same overall pattern was observed in the 'authority to prescribe' data. From 2000-2002, prescribing of the starter pack (3 x 100 mg loading dose plus 30 x 20 mg tablets) declined (down 74%); likewise for the 20mg (30 tablets) pack. Gradual increases were noted for the 10 mg (30 tablets) pack (up 40%). Approximately 135 reports, detailing about 370 individual ADR, were generated annually. Gastro-intestinal disorders predominated, accounting for 24% of reactions reported to ADRAC. Skin and appendages disorders constituted 14% of reported reactions. Deaths in leflunomide users were attributed to a combination of haematological and gastro-intestinal complications, but it was not possible to ascertain other medication usage or contributing factors. Trends observed with the ADRAC reports were consistent with the WHO database. Conclusions Leflunomide was the first registered DMARD in Australia in over a decade and its use has increased within the community. The ADR reports might have contributed to Australian rheumatologists gradually abandoning loading patients with high doses of leflunomide in favour of starting therapy at lower doses. Copyright (c) 2006 John Wiley & Sons, Ltd.

Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas

TSLC1 (tumor suppressor in lung cancer-1, IGSF4) encodes a member of the immunoglobulin superfamily molecules, which is involved in cell-cell adhesion. TSLC1 is connected to the actin cytoskeleton by DAL-1 (differentially expressed in adenocarcinoma of the lung-1, EPB41L3) and it directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large. Recent data suggest that aberrant promoter methylation is important for TSLC1 inactivation in lung carcinomas. However, little is known about the other two genes in this cascade, DAL-1 and MPP3. Thus, we investigated the expression and methylation patterns of these genes in lung cancer cell lines, primary lung carcinomas and nonmalignant lung tissue samples. By reverse transcription-polymerase chain reaction, loss of TSLC1 expression was observed in seven of 16 (44%) non-small-cell lung cancer (NSCLC) cell lines and in one of 11 (9%) small-cell lung cancer (SCLC) cell lines, while loss of DAL- 1 expression was seen in 14 of 16 (87%) NSCLC cell lines and in four of 11 (36%) SCLC cell lines. By contrast, MPP3 expression was found in all tumor cell lines analysed. Similar results were obtained by microarray analysis. TSLC1 methylation was seen in 13 of 39 (33%) NSC LC cell lines, in one of 11 (9%) SCLC cell lines and in 100 of 268 (37%) primary NSCLCs. DAL-1 methylation was observed in 17 of 39 (44%) NSCLC cell lines, in three of 11 (27%) SCLC cell lines and in 147 of 268 (55%) primary NSCLCs. In tumors of NSCLC patients with stage II-III disease, DAL-1 methylation was seen at a statistically significant higher frequency compared to tumors of patients with stage I disease. A significant correlation between loss of expression and methylation of the genes in lung cancer cell lines was found. Overall, 65% of primary NSCLCs had either TSLC1 or DAL-1 methylated. Methylation of one of these genes was detected in 59% of NSCLC cell lines; however, in SCLC cell lines, methylation was much less frequently observed. The majority of nonmalignant lung tissue samples was not TSLC1 and DAL-1 methylated. Re-expression of TSLC1 and DAL-1 was seen after treatment of lung cancer cell lines with 5-aza-2$-deoxy-cytidine. Our results suggest that methylation of TSLC1 and/or DAL-1, leading to loss of their expression, is an important event in the pathogenesis of NSCLC.