Effect of an attentional strategy on movement-related potentials recorded from subjects with Huntington's disease

Huntington's disease patients perform automatic movements in a bradykinetic manner, somewhat similar to patients with Parkinson's disease. Cortical activity relating to the preparation of movement in Parkinson's disease is significantly improved when a cognitive strategy is used. It is unknown whether patients with Huntington's disease can utilise an attentional strategy, and what effect this strategy would have on the premovement cortical activity. Movement-related potentials were recorded from 12 Huntington's disease patients and controls performing externally cued finger tapping movement, allowing an examination of cortical activity related to movement performance and bradykinesia in this disease. All subjects were tested in two conditions, which differed only by the presence or absence of the cognitive strategy. The Huntington's disease group, unlike controls, did not produce a rising premovement potential in the absence of the strategy. The Huntington's disease group did produce a rising premovement potential for the strategy condition, but the early slope of the potential was significantly reduced compared with the control group's early slope. These results are similar to those found previously with Parkinson's disease patients. The strategy may have put the task, which previously might have been under deficient automatic control, under attentional control. (C) 2002 Movement Disorder Society.

Resolution and characterisation of multiple isoforms of bovine kappa-casein by 2-DE following a reversible cysteine-tagging enrichment strategy

Visualisation of multiple isoforms of kappa-casein on 2-D gels is restricted by the abundant alpha- and beta-caseins that not only limit gel loading but also migrate to similar regions as the more acidic kappa-casein isoforms. To overcome this problem, we took advantage of the absence of cysteine residues in alpha(S1)- and beta-casein by devising an affinity enrichment procedure based on reversible biotinylation of cysteine residues. Affinity capture of cysteine-containing proteins on avidin allowed the removal of the vast majority of alpha(S1)- and beta-casein, and on subsequent 2-D gel analysis 16 gel spots were identified as kappa-casein by PMF. Further analysis of the C-terminal tryptic peptide along with structural predictions based on mobility on the 2-D gel allowed us to assign identities to each spot in terms of genetic variant (A or B), phosphorylation status (1, 2 or 3) and glycosylation status (from 0 to 6). Eight isoforms of the A and B variants with the same PTMs were observed. When the casein fraction of milk from a single cow, homozygous for the B variant of kappa-casein, was used as the starting material, 17 isoforms from 13 gel spots were characterised. Analysis of isoforms of low abundance proved challenging due to the low amount of material that could be extracted from the gels as well as the lability of the PTMs during MS analysis. However, we were able to identify a previously unrecognised site, T-166, that could be phosphorylated or glycosylated. Despite many decades of analysis of milk proteins, the reasons for this high level of heterogeneity are still not clear.

Presence-absence versus abundance data for monitoring threatened species

Effective detection of population trend is crucial for managing threatened species. Little theory exists, however, to assist managers in choosing the most cost-effective monitoring techniques for diagnosing trend. We present a framework for determining the optimal monitoring strategy by simulating a manager collecting data on a declining species, the Chestnut-rumped Hylacola (Hylacola pyrrhopygia parkeri), to determine whether the species should be listed under the IUCN (World Conservation Union) Red List. We compared the efficiencies of two strategies for detecting trend, abundance, and presence-absence surveys, underfinancial constraints. One might expect the abundance surveys to be superior under all circumstances because more information is collected at each site. Nevertheless, the presence-absence data can be collected at more sites because the surveyor is not obliged to spend a fixed amount of time at each site. The optimal strategy for monitoring was very dependent on the budget available. Under some circumstances, presence-absence surveys outperformed abundance surveys for diagnosing the IUCN Red List categories cost-effectively. Abundance surveys were best if the species was expected to be recorded more than 16 times/year; otherwise, presence-absence surveys were best. The relationship between the strategies we investigated is likely to be relevant for many comparisons of presence-absence or abundance data. Managers of any cryptic or low-density species who hope to maximize their success of estimating trend should find an application for our results.

A two-phase strategy for detecting recombination in nucleotide sequences

Genetic recombination can produce heterogeneous phylogenetic histories within a set of homologous genes. Delineating recombination events is important in the study of molecular evolution, as inference of such events provides a clearer picture of the phylogenetic relationships among different gene sequences or genomes. Nevertheless, detecting recombination events can be a daunting task, as the performance of different recombination-detecting approaches can vary, depending on evolutionary events that take place after recombination. We previously evaluated the effects of post-recombination events on the prediction accuracy of recombination-detecting approaches using simulated nucleotide sequence data. The main conclusion, supported by other studies, is that one should not depend on a single method when searching for recombination events. In this paper, we introduce a two-phase strategy, applying three statistical measures to detect the occurrence of recombination events, and a Bayesian phylogenetic approach to delineate breakpoints of such events in nucleotide sequences. We evaluate the performance of these approaches using simulated data, and demonstrate the applicability of this strategy to empirical data. The two-phase strategy proves to be time-efficient when applied to large datasets, and yields high-confidence results.

Papillomavirus virus-like particles can deliver defined CTL epitopes to the MHC class I pathway

To evaluate an antigen delivery system in which exogenous antigen can target the major histocompatibility complex (MHC) class I pathway, a single human papillomavirus (HPV) 16 E7 cytotoxic T lymphocyte (CTL) epitope and a single HIV gp160 CTL epitope were separately fused to the C-terminus or bovine papillomavirus 1 (BPV1) L1 sequence to form hybrid BPV1L1 VLPs. Mice immunized with these hybrid VLPs mounted strong CTL responses against the relevant target cells in the absence of any adjuvants. In addition, the CTL responses induced by immunization with BPV1L1/HPV16E7CTL VLPs protected mice against challenge with E7-transformed tumor cells. Furthermore, a high titer-specific antibody response against BPV1L1 VLPs was also induced, and this antiserum could inhibit papillomavirus-induced agglutination of mouse erythrocytes, suggesting that the antibody may recognize conformational determinates relevant to virus neutralization. These data demonstrate that hybrid BPV1L1 VLPs can be used as carriers to target antigenic epitopes to both the MHC class I and class II pathways, providing a promising strategy for the design of vaccines to prevent virus infection, with the potential to elicit therapeutic virus-specific CTL responses. (C) 1998 Academic Press.

The meeting place problem: Salience and search.

The notion of salience was developed by Schelling in the context of the meeting-place problem of locating a partner in the absence of a pre-agreed meeting place. In this paper, we argue that a realistic specification of the meeting place problem involves allowing a strategy of active search over a range of possible meeting places. We solve this extended problem, allowing for extensions such as repeated play, search costs and asymmetric payoffs. The result is a considerably richer, but more complex, notion of salience. (C) 1998 Elsevier Science B.V.

Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination

Development of CD8 alpha beta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes, Here we describe a DNA plasmid encoding a polyepitope or polytope protein, which contained multiple contiguous minimal murine CTL epitopes, Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models, CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help, The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.

Renewing Australia's mental health strategy

The Second National Mental Health Plan, endorsed by Commonwealth, State and Territory governments on 30 July 1998, will pursue three key themes: (1) Promoting mental health, plus prevention of and early intervention in mental disorders, with a specific focus on depression; (2) continuing structural reform of mental health services, including better integration with general practice and the private psychiatric sector; and (3) implementing quality and outcome measures in mental health services, including evidence-based practice.

A bleach program for inmates in NSW: an HIV prevention strategy

Syringe cleaning guidelines for injecting drug users (IDUs) were revised in 1993. This paper examines efforts by IDUs in NSW prisons to adopt the revised guidelines in 1994. Consecutive inmates (229) nearing release were visited and asked to call a toll free number for an interview once released. Respondents (102) did not differ from non-respondents (127). Many respondents (64%) reported ever injecting and many of these reported injecting (58%), sharing (48%) and syringe cleaning (46%) when last in prison. Some (23%) respondents reported adopting the revised syringe cleaning guidelines. Tattooing (38%) was reported more often than sexual activity in prison (4%). A new methodology for prison research was found to be feasible in this study. The potential for HIV to spread in prison still poses major public health challenges.

Chemical synthesis and folding pathways of large cyclic polypeptide: Studies of the cystine knot polypeptide kalata B1

Kalata B1 is a member of a new family of polypeptides, isolated from. plants, which have a cystine knot structure embedded within an amide-cyclized backbone. This family of molecules are the largest known cyclic peptides, and thus, the mechanism of synthesis and folding is of great interest. To provide information about both these phenomena, we have synthesized kalata B1 using two distinct strategies. In the first, oxidation of the cysteine residues of a linear precursor peptide to form the correct disulfide bonds results in folding of the three-dimensional structure and preorganization of the termini in close proximity for subsequent cyclization. The second approach involved cyclization prior to oxidation. In the first method, the correctly folded peptide was produced only in the presence of partially hydrophobic solvent conditions. These conditions are presumably required to stabilize the surface-exposed hydrophobic residues. However,; in the synthesis,involving cyclization prior to oxidation, the cyclic reduced peptide folded to a significant degree in the absence of hydrophobic solvents and even more efficiently in the presence of hydrophobic solvents. Cyclization clearly has a major effect on the folding pathway and facilitates formation of the correctly disulfide-bonded form in aqueous solution; In addition to facilitating folding to a compact stable structure cyclization has an important effect on biological activity as assessed by hemolytic activity.

Protein sequence threading, the alignment problem, and a two-step strategy

Conventionally, protein structure prediction via threading relies on some nonoptimal method to align a protein sequence to each member of a library of known structures. We show how a score function (force field) can be modified so as to allow the direct application of a dynamic programming algorithm to the problem. This involves an approximation whose damage can be minimized by an optimization process during score function parameter determination. The method is compared to sequence to structure alignments using a more conventional pair-wise score function and the frozen approximation. The new method produces results comparable to the frozen approximation, but is faster and has fewer adjustable parameters. It is also free of memory of the template's original amino acid sequence, and does not suffer from a problem of nonconvergence, which can be shown to occur with the frozen approximation. Alignments generated by the simplified score function can then be ranked using a second score function with the approximations removed. (C) 1999 John Wiley & Sons, Inc.

Moisture is required for the termination of egg diapause in the chrysomelid beetle, Homichloda barkeri

Four factors (moisture, light regime, temperature, food type) were examined for their effects on the embryonic diapause of Homichloda (Weiseana) barkeri (Jacoby) (Coleoptera: Chrysomelidae), a biocontrol agent for prickly acacia, Acacia nilotica (L.) Willdenew ex Delile (Mimosaceae). Moisture is critical for termination of diapause. A single wetting of eggs resulted in a low hatch rate while a sequence of wetting events followed by periods of dryness produced a high hatch rate. A relatively constant proportion of embryos within each batch initiated development at each wetting event, with hatching complete after the eighth wetting event in these trials. An extended interval between wetting events, tested at up to 23 days, did not result in a decreased overall hatch rate. A threshold time of exposure to moisture of between 3 to 6 h is required before development proceeds. The response of eggs to the moisture regime is seen as a strategy for taking advantage of available food after rainfall by terminating diapause, rather than merely a quiescent response to the absence of moisture. Temperature affected development time and the proportion of eggs that developed. Experimental manipulations of photoperiod and host-plant availability showed no effect on embryonic development.