All-atom generalized-ensemble simulations of small proteins

We give an overview of some generalized-ensemble techniques that have proven successful in all-atom simulations of proteins. We show that these techniques enable efficient investigations of secondary structure formation and folding in peptides and small proteins. Results are presented for various alanine-based artificial peptides and a small protein, the 36-residued villin headpiece subdomain (HP-36). Our results indicate that all-atom simulations of proteins may be more restricted by the accuracy of the present energy functions than by the efficiency of the search algorithms.     

Virus Matryoshka: A Bacteriophage Particle—Guided Molecular Assembly Approach to a Monodisperse Model of the Immature Human Immunodeficiency Virus

Immature human immunodeficiency virus type 1 (HIV‐1) is approximately spherical, but is constructed from a hexagonal lattice of the Gag protein. As a hexagonal lattice is necessarily flat, the local symmetry cannot be maintained throughout the structure. This geometrical frustration presumably results in bending stress. In natural particles, the stress is relieved by incorporation of packing defects, but the magnitude of this stress and its significance for the particles is not known. In order to control this stress, we have now assembled the Gag protein on a quasi‐spherical template derived from bacteriophage P22. This template is monodisperse in size and electron‐transparent, enabling the use of cryo‐electron microscopy in structural studies. These templated assemblies are far less polydisperse than any previously described virus‐like particles (and, while constructed according to the same lattice as natural particles, contain almost no packing defects). This system gives us the ability to study the relationship between packing defects, curvature and elastic energy, and thermodynamic stability. As Gag is bound to the P22 template by single‐stranded DNA, treatment of the particles with DNase enabled us to determine the intrinsic radius of curvature of a Gag lattice, unconstrained by DNA or a template. We found that this intrinsic radius is far larger than that of a virion or P22‐templated particle. We conclude that Gag is under elastic strain in a particle; this has important implications for the kinetics of shell growth, the stability of the shell, and the type of defects it will assume as it grows.     

The complexities of complex span: Explaining individual differences in working memory in children and adults.

Two studies are presented that investigated the constraints underlying working memory performance in children and adults. In each case, independent measures of processing efficiency and storage capacity are assessed to determine their relative importance in predicting performance on complex span tasks, which measure working memory capacity. Results show that complex span performance was independently constrained by individual differences in dornain-general processing efficiency and domain-specific storage capacity. Residual variance, which may reflect the ability to coordinate storage and processing, also predicted academic achievement. These results challenge the view that complex span taps, a limited-capacity resource pool shared between processing and storage operations. Rather, they are consistent with a multiple-component model in which separate resource pools support the processing and storage functions of working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Image charge detection mass spectrometry: pushing the envelope with sensitivity and accuracy

A novel image charge detection mass spectrometer (CDMS) with improved sensitivity and mass accuracy is described. The improved detector design and method of data analysis allow us to measure a reliable mass for a single macroion that is an order of magnitude smaller than previously achieved with CDMS. The apparatus employs an image charge detector array consisting of 22 detectors. The detectors are divided into two groups that can be floated at different potentials. The signals from the detector array are analyzed using a correlation approach to yield the velocities in the two groups of detectors and the charge. These quantities, together with the voltage difference between the two groups of detectors, provide a value for the mass. The mass, m/z, and charge distributions recorded for 300 kDa poly(ethylene oxide) (PEG) are presented. The mass distribution shows a peak at around 300 kDa with a width close to that expected from the polymer size distribution. In addition, there are broad peaks in the mass distribution at around 100 and 500 MDa. The 300 kDa ions have m/z ratios of ～2 kDa/e, and the 100 and 500 MDa ions have m/z ratios of ～40 kDa/e. The 100 and 500 MDa ions probably result from PEG aggregates that are either present in solution or the residue of large electrospray droplets.     

Do two separate speech measures contrain verbal short-term memory in children?

Previous research has indicated that 2 processing rates may constrain verbal short-term memory performance. These have been linked to individual differences in (a) the time taken to articulate spoken words and (b) the duration of pauses that occur between words in the output responses to memory tasks. Two experiments examined whether evidence for these effects on memory can be obtained for measures taken from a single speech sample. Children articulated pairs of words as rapidly as possible. In both experiments, the spoken duration of words and the length of the pauses between them predicted significant variance in verbal short-term memory performance. It is argued that the duration of words is linked to memory performance through the processes underlying time-based forgetting in short-term memory. In contrast, the duration of pauses in speeded articulation may index individual differences in speech planning processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Linking theory of mind and central coherence bias in autism and in the general population.

Three experiments investigated whether 2 characteristic aspects of the psychological profile of autism, theory-of-mind deficits and weak central coherence, might be functionally related. Experiment 1 showed that in the general population, performance on a proposed test of theory of mind was inversely related to speed on the Embedded Figures Test, a measure of central coherence bias. Experiments 2 and 3 confirmed that poor theory-of-mind performance was linked to weak central coherence among typically developing children and among children with autism; however, the correlations between these measures were reliable only after accounting for differences in individuals' verbal mental ages. This pattern of results is interpreted in terms of a relationship between individual differences in theory of mind and central coherence bias, a relationship that is separate from any developmental differences in these domains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An IMS-IMS analogue of MS-MS

The development of a new ion mobility/mass spectrometry instrument that incorporates a multifield drift tube/ion funnel design is described. In this instrument, individual components from a mixture of ions can be resolved and selected on the basis of mobility differences prior to collisional activation inside the drift tube. The fragment ions that are produced can be dispersed again in a second ion mobility spectrometry (IMS) region prior to additional collisional activation and MS analysis. The result is an IMS-IMS analogue of MS-MS. Here, we describe the preliminary instrumental design and experimental approach. We illustrate the approach by examining the highly characterized bradykinin and ubiquitin systems. Mobility-resolved fragment ions of bradykinin show that b-type ions are readily discernible fragments, because they exist as two easily resolvable structural types. Current limitations and future directions are briefly discussed.     

Verbal and nonverbal abilities in the Williams syndrome phenotype: evidence for diverging developmental trajectories

One commonly cited feature of Williams syndrome is a characteristic dissociation between relatively spared language skills and severely impaired nonverbal abilities. However, the actual evidence for a dissociation between verbal and nonverbal abilities in Williams syndrome is equivocal. In two separate studies we examined these abilities in 16 individuals showing the Williams syndrome phenotype. When considered as a whole, the group did have significantly superior verbal abilities, but this difference was caused by a large discrepancy in abilities in only a small number of individuals. In both studies there was a clear, linear relation between individuals' verbal ability, and the magnitude of their verbal-nonverbal discrepancy. We suggest that these results are best explained in terms of verbal ability developing at a faster rate than nonverbal ability in this disorder. We discuss how this model of differential rates of development has the potential to reconcile the apparently inconsistent findings in this area.     

What are the causes of reduced fit in scaling and clustering studies of semantic proximity data, and how else to measure them: A comment on Storms et al. (2003).

G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003) noted that the goodness-of-fit indices for scaling and clustering solutions of proximity data from populations with hypothesized semantic deficits tend to be reduced in comparison with control participants, and that this precludes an unambiguous interpretation of such data. However, this effect is not necessarily as inconsistent with the proposal of semantic degradation in these groups, or as consistent with explanations in terms of access or attentional problems, as is suggested by G. Storms et al. Also, although performance on word fluency tasks is certainly constrained by the ability to access stored information, there are ways in which this confounding influence may be controlled for in the study of semantic deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)