Thermodynamic analysis of autonomous parallel beta-sheet formation in water.

We report the first thermodynamic analysis of parallel beta-sheet formation in a model system that folds in aqueous solution. NMR chemical shifts were used to determine beta-sheet population, and van't Hoff anaysis provided thermodynamic parameters. Our approach relies upon the d-prolyl-1,1-dimethyl-1,2-diaminoethane unit to promote parallel beta-sheet formation between attached peptide strands.

Verbal repetition in patients with Alzheimer's disease who receive donepezil.

Background: Current outcome measures for Alzheimer's disease (AD) drugs have been criticized as insufficiently patient-centred. One commonly unmeasured goal of patients and caregivers is verbal repetition.

Objectives: We examined how often reducing repetition (of questions, statements or stories) was set as treatment goal, whether and when it responded, and how change in repetition correlated with change in other domains.

Users' perceptions of the risks and effects of taking ecstasy (MDMA): a questionnaire study.

This self-report questionnaire study examined ecstasy users' perceptions of the risks associated with their use of ecstasy, their precautions against such risks, and its perceived effects on their lives. Gender differences in these areas were also explored. The sample comprised 328 ecstasy users (139 female, 187 male, one transsexual) with a mean age of 22.

Interactions of the cellular CCAAT displacement protein and human papillomavirus E2 protein with the viral origin of replication can regulate DNA replication.

Previously, we and others have shown that CCAAT displacement protein (CDP) negatively regulates the papillomavirus promoters. Overexpression of CDP has been shown to inhibit high-risk human papillomavirus virus (HPV) and bovine papillomavirus DNA replication in vivo presumably through reduction in expression of viral replication proteins, E1 and E2. Sequence analysis of the HPV origin indicates several potential CDP-binding sites with one site overlapping the E1-binding site.

Papillomavirus E1 protein binds to and stimulates human topoisomerase I.

The papillomavirus (PV) E1 helicase plays a direct role in recruiting cellular DNA replication factors, such as replication protein A or polymerase alpha-primase, to replicate PV genomes. Here, E1 is shown to bind to human topoisomerase I and stimulate its relaxation activity up to sevenfold. The interaction between E1 and topoisomerase I was mapped to the E1 DNA binding domain and C terminus.

Disconnection of language and memory in semantic dementia: a comparative and theoretical analysis.

In this paper, we present an illustrative case of Semantic Dementia (SD) and we review the literature on this relatively rare progressive neurodegenerative disorder. After reviewing the clinical, neuroimaging, neuropathological, and genetic features of SD, we propose a theoretical framework that addresses features of SD and relates them to features of other well known neuropsychiatric syndromes. Our 'on-line / off-line disconnection' model seeks to conceptualize SD as a syndrome of disconnection between two large distributed cortical networks, namely, between those networks that subserve language function and those that subserve memory function.

Reasoning about conjunctive probabilistic concepts in childhood.

While adults are known to exhibit biases when making conjunctive probability judgments, little is known about childhood competencies in this area. Participants (aged between four and five years, eight and ten years, and a group of young adults) attempted to select the more likely of two events, a single event, and a conjunctive event containing, as one of its components, the single event. The problems were such that the objective probabilities of the component events were potentially available.

APOE genotype, vascular risk factors, memory test performance and the five-year risk of vascular cognitive impairment or Alzheimer's disease.

The APOE epsilon4 gene and poor memory test performance have each been associated with an increased risk of developing dementia, but the relationship between these risk factors in predicting dementia is unclear. We examined the multivariate effects of APOE genotype, memory test performance and vascular risk factors in predicting incident Alzheimer's disease (AD) and vascular cognitive impairment (VCI) in the Canadian Study of Health and Aging. Delayed free recall was measured by the Buschke Cued Recall Test (BCRT).

Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid arthritis.

Objective: The cause of neurologic (N) and psychiatric (P) syndromes in patients with systemic lupus erythematosus (SLE) is mutifactorial and includes primary immunopathogenic mechanisms, nonspecific sequelae of chronic disease, and concurrent illnesses. We compared the prevalence, diversity, and clinical significance of NP syndromes in patients with SLE and rheumatoid arthritis (RA).

Methods: Fifty-three patients with SLE were matched by age and sex to 53 patients with RA attending ambulatory clinics in a single academic medical center.

Reasoning deficits in ecstasy (MDMA) polydrug users.

Rationale/objectives: Previous research has shown that ecstasy users are impaired in thinking and reasoning. The present study sought to explore the possibility that syllogistic reasoning errors in ecstasy users were due to an inability to construct a model of the premises due to working memory limitations.

Methods: Twenty-nine ecstasy users and 25 nonecstasy user controls completed abstract syllogistic reasoning problems varying in difficulty.

The differential effects of ecstasy/polydrug use on executive components: shifting, inhibition, updating and access to semantic memory.

Rationale/objectives: Recent theoretical models suggest that the central executive may not be a unified structure. The present study explored the nature of central executive deficits in ecstasy users.

Methods: In study 1, 27 ecstasy users and 34 non-users were assessed using tasks to tap memory updating (computation span; letter updating) and access to long-term memory (a semantic fluency test and the Chicago Word Fluency Test).

Syllogistic reasoning performance in MDMA (Ecstasy) users.

Previous research has demonstrated working memory and executive deficits in recreational users of MDMA (3,4-methylenedioxymethamphetamine; Ecstasy). In turn, both of these constructs have been implicated in syllogistic reasoning performance. Twenty-two MDMA users (mean age = 21.

Age-related impairment in executive functioning: updating, inhibition, shifting, and access.

Miyake, Friedman, Emerson, Witzki, Howerter and Wager (2000) have argued that the central executive is fractionated consisting of at least three separable component processes: updating, shifting, and inhibition. The Wisconsin Card Sort Test, random letter generation, Brooks spatial sequences, reading and computation span, word fluency, and a measure of dual task performance were administered to 95 individuals aged between 20 and 81, average age 41.89.

The nature of ecstasy-group related deficits in associative learning.

Rationale/objectives: Research has revealed associative learning deficits among users of ecstasy; the present study explored the component processes underlying these deficits.

Methods: Thirty-five ecstasy users and 62 non-ecstasy users completed a computer-based, verbal paired-associates learning task. Participants attempted to learn eight sequentially presented word pairs.

Visuo-spatial working memory deficits in current and former users of MDMA ('ecstasy').

Verbal working memory and executive deficits have been observed in ecstasy users. The present study sought to establish whether these also extended to visuo-spatial working memory. Thirty-six current ecstasy users, 12 former users (abstinent for at least 6 months) and 31 individuals that had never used ecstasy were tested on a maintenance plus type visuo-spatial working memory task.

Evidence for executive deficits among users of MDMA (Ecstasy).

Random letter generation and computation span are tasks known to load on executive, prefrontal resources. Previous research suggests that Ecstasy users are impaired on random letter generation. The current study, employing a larger sample (44 current Ecstasy users, and 59 non-Ecstasy users), together with more effective statistical controls for other drug use, failed to replicate previous findings.

Flow cytometric DNA ploidy analysis of peripheral blood from patients with sezary syndrome: detection of aneuploid neoplastic T cells in the blood is associated with large cell transformation in tissue.

We reviewed and screened 219 cutaneous T-cell lymphoma (CTCL) cases for Sezary syndrome (SS); 63 met the criteria for SS. Of these, 17 (27%) demonstrated circulating aneuploid cells and 46 (73%) showed only euploid cells in blood samples. Of 17 aneuploid cases, DNA ploidy study was essential for initial blood-based diagnosis of SS in 4 (24%) and important in monitoring minimal residual disease after treatment in 9 (53%) in which neoplastic T cells showed otherwise unremarkable or nonspecific flow cytometric immunophenotypic findings.

Eosinophilic dysplasia of the cervix: a newly recognized variant of cervical squamous intraepithelial neoplasia.

A proportion of cervical squamous intraepithelial lesions encountered in surgical pathology practice contain both metaplastic features and some degree of atypia [so-called eosinophilic dysplasia (ED)] that defy classification according to established criteria. To elucidate the nature of these lesions, we compared 44 cases of ED to 20 classic high-grade squamous intraepithelial lesions (HSILs) and 10 squamous metaplasias using a panel of biomarkers and human papillomavirus (HPV) testing. EDs were defined as 1) lack of normal maturation; 2) relatively abundant eosinophilic cytoplasm and distinct cell borders compared with conventional HSIL; 3) mildly to moderately increased nuclear to cytoplasmic ratio; and 4) focal dysplastic nuclei showing nuclear enlargement, hyperchromasia, variable nuclear membrane irregularities, and appreciable nucleoli.

Secondary structural preferences of 2,2-disubstituted pyrrolidine-4-carboxylic acid oligomers: beta-peptide foldamers that cannot form internal hydrogen bonds.

We examine a new class of beta-peptides, 2,2-disubstituted pyrrolidine-4-carboxylic acid oligomers, and show that they manifest discrete conformational preferences despite the impossibility of internal hydrogen bonding. Numerous beta-peptide families have been described that display specific secondary structural preferences, but all of the conformations characterized in detail so far have contained internal hydrogen bonds. Internal hydrogen bonding is observed within the most common secondary structures of conventional peptides as well.

Hydrophobic core repacking in a coiled-coil dimer via phage display: insights into plasticity and specificity at a protein-protein interface.

The coiled-coil, which consists of two or more interwoven amphiphilic alpha-helices, is formed by sequences that have a characteristic heptad repeat (abcdefg) where a and d are hydrophobic residues. Most efforts to elucidate the origins of coiled-coil pairing selectivity have focused on electrostatic interactions among side chains that flank the core (positions e and g) and on polar side chains that occur occasionally at core positions. We have used phage display to explore another source of coiled-coil specificity: steric matching among nonpolar side chains in the core.

Dyslexic students have more everyday cognitive lapses.

There is a dearth of information about the everyday performance difficulties of adult dyslexic people. This study investigates the empirical support for anecdotal reports of increased vulnerability to distraction in dyslexia, using the self-report Cognitive Failures Questionnaire (CFQ). Two groups of university students, a dyslexic group and a non-dyslexic control group, were asked to complete the CFQ.

Verbal working memory deficits in current and previous users of MDMA.

Previous research suggests that MDMA users are impaired in various aspects of cognitive functioning, however, it remains unclear whether they might experience deficits in established measures of verbal working memory functioning. In the present study current and previous MDMA users were compared with non-users on verbal working memory measures including reading and computation span. Both user groups were found to be impaired on the computation span measure while current users also exhibited impairment in reading span.

Biomechanic characteristics of patients with spastic and dystonic hypertonia in cerebral palsy.

Objective: To determine what biomechanic characteristics of knee joint motion and walking show potential to quantitatively differentiate spasticity and dystonia in cerebral palsy (CP).

Design: Descriptive measurement study.

Setting: University hospital.

Visuospatial memory impairments in users of MDMA ('ecstasy').

Rationale: Previous studies have presented conflicting findings regarding visuospatial span deficits in MDMA ('ecstasy') users, possibly attributable to a lack of distinction between simple visuospatial span and visuospatial working memory span. Both draw upon central executive processing, while the latter also involves concurrent goal-orientated visuospatial processing.

Objectives: This study compared visuospatial working memory span for MDMA users and controls.

Variations in case definition affect prevalence but not outcomes of mild cognitive impairment.

Objective: To examine the prevalence estimates and 5-year outcomes of various case definitions of mild cognitive impairment (MCI).

Methods: The authors examined 1,790 adults 65 years of age or older who completed neuropsychological and clinical assessments in the Canadian Study of Health and Aging, a 5-year, representative, prospective cohort study.

Results: The most commonly used case definition of MCI yielded a population prevalence estimate of 1.