Potential Anticancer Compounds. III, Synthesis of Some 8-Substituted Caffeines and Theophyllines

Author Institution: Department of Chemistry, University of Cincinnati, Cincinnati 21, Ohi

Influence of hand position on the near-effect in 3D attention

Voluntary reorienting of attention in real depth situations is characterized by an attentional bias to locations near the viewer once attention is deployed to a spatially cued object in depth. Previously this effect (initially referred to as the ‘near-effect’) was attributed to access of a 3D viewer-centred spatial representation for guiding attention in 3D space. The aim of this study was to investigate whether the near-bias could have been associated with the position of the response-hand, always near the viewer in previous studies investigating endogenous attentional shifts in real depth. In Experiment 1, the response-hand was placed at either the near or far target depth in a depth cueing task. Placing the response-hand at the far target depth abolished the near-effect, but failed to bias spatial attention to the far location. Experiment 2 showed that the response-hand effect was not modulated by the presence of an additional passive hand, whereas Experiment 3 confirmed that attentional prioritization of the passive hand was not masked by the influence of the responding hand on spatial attention in Experiment 2. The pattern of results is most consistent with the idea that response preparation can modulate spatial attention within a 3D viewer-centred spatial representation

Identification of direct residue contacts in protein-protein interaction by message passing

Understanding the molecular determinants of specificity in protein-protein interaction is an outstanding challenge of postgenome biology. The availability of large protein databases generated from sequences of hundreds of bacterial genomes enables various statistical approaches to this problem. In this context covariance-based methods have been used to identify correlation between amino acid positions in interacting proteins. However, these methods have an important shortcoming, in that they cannot distinguish between directly and indirectly correlated residues. We developed a method that combines covariance analysis with global inference analysis, adopted from use in statistical physics. Applied to a set of >2,500 representatives of the bacterial two-component signal transduction system, the combination of covariance with global inference successfully and robustly identified residue pairs that are proximal in space without resorting to ad hoc tuning parameters, both for heterointeractions between sensor kinase (SK) and response regulator (RR) proteins and for homointeractions between RR proteins. The spectacular success of this approach illustrates the effectiveness of the global inference approach in identifying direct interaction based on sequence information alone. We expect this method to be applicable soon to interaction surfaces between proteins present in only 1 copy per genome as the number of sequenced genomes continues to expand. Use of this method could significantly increase the potential targets for therapeutic intervention, shed light on the mechanism of protein-protein interaction, and establish the foundation for the accurate prediction of interacting protein partners.Comment: Supplementary information available on http://www.pnas.org/content/106/1/67.abstrac

Primate modularity and evolution: first anatomical network analysis of primate head and neck musculoskeletal system

Network theory is increasingly being used to study morphological modularity and integration. Anatomical network analysis (AnNA) is a framework for quantitatively characterizing the topological organization of anatomical structures and providing an operational way to compare structural integration and modularity. Here we apply AnNA for the first time to study the macroevolution of the musculoskeletal system of the head and neck in primates and their closest living relatives, paying special attention to the evolution of structures associated with facial and vocal communication. We show that well-defined left and right facial modules are plesiomorphic for primates, while anthropoids consistently have asymmetrical facial modules that include structures of both sides, a change likely related to the ability to display more complex, asymmetrical facial expressions. However, no clear trends in network organization were found regarding the evolution of structures related to speech. Remarkably, the increase in the number of head and neck muscles – and thus of musculoskeletal structures – in human evolution led to a decrease in network density and complexity in humans

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

An Examination of the Effects of Mindfulness and Task-Relevant Attentional Focus on Running Performance

The purpose of the current study was to investigate the effect of mindfulness and task-relevant attentional focus on running performance. WKU psychology undergraduate students were assigned to one of two conditions: task-relevant attentional focus experimental training and no training control. Participants in the experimental condition received training designed to optimize the use of attentional focus strategies in a running context. Trait level mindfulness was examined as a covariate. Participants were compared on two mile run times and the use of attentional focus strategies. Differences were expected to reveal the effectiveness of the training by showing faster running times in the experimental group, and higher use of task-relevant attentional focus strategies. Only higher use of task-relevant attentional focus strategies, specifically focus on bodily sensation was supported by the data. Explanations of the results as well as exploratory analyses are provided in addition to suggestions for future research

Joint analysis of transcriptional and post- transcriptional brain tumor data: searching for emergent properties of cellular systems

<p>Abstract</p> <p>Background</p> <p>Advances in biotechnology offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. However, to date, most computational and algorithmic efforts have been directed at mining data from each of these molecular <it>levels </it>(genomic, transcriptional, etc.) separately. In view of the rapid advances in technology (new generation sequencing, high-throughput proteomics) it is important to address the problem of analyzing these data as a whole, i.e. preserving the emergent properties that appear in the cellular system when all molecular levels are interacting. We analyzed one of the (currently) few datasets that provide both transcriptional and post-transcriptional data of the same samples to investigate the possibility to extract more information, using a joint analysis approach.</p> <p>Results</p> <p>We use Factor Analysis coupled with pre-established knowledge as a theoretical base to achieve this goal. Our intention is to identify structures that contain information from both mRNAs and miRNAs, and that can explain the complexity of the data. Despite the small sample available, we can show that this approach permits identification of meaningful structures, in particular two polycistronic miRNA genes related to transcriptional activity and likely to be relevant in the discrimination between gliosarcomas and other brain tumors.</p> <p>Conclusions</p> <p>This suggests the need to develop methodologies to simultaneously mine information from different levels of biological organization, rather than linking separate analyses performed in parallel.</p

The Impact of a Camp Orientation Program on First-Year Academic Engagement and Persistence

More and more, institutions of higher education are being held accountable for student success measures such as persistence and completion rates. If research indicates that higher levels of student engagement lead to better academic outcomes, it is then reasonable to equate this to improved retention and graduation rates. The present study presents findings associated with a camp orientation program for first-year students and its impact on levels of academic engagement and persistence. Data collected from the Beginning College Survey of Student Engagement (BCSSE) and National Survey of Student Engagement (NSSE) were used to determine if statistically significant differences exist between camp participants and non-participants. Findings indicate no statistically significant difference between camp participants and non-participants on NSSE benchmarks related to academic satisfaction, enriching educational experiences, student-faculty engagement or persistence from fall to spring of the first college year