Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells.

The growth of stem cells can be modulated by physical factors such as extracellular matrix nanotopography. We hypothesize that nanotopography modulates cell behavior by changing the integrin clustering and focal adhesion (FA) assembly, leading to changes in cytoskeletal organization and cell mechanical properties. Human mesenchymal stem cells (hMSCs) cultured on 350 nm gratings of tissue-culture polystyrene (TCPS) and polydimethylsiloxane (PDMS) showed decreased expression of integrin subunits alpha2, alpha , alpha V, beta2, beta 3 and beta 4 compared to the unpatterned controls. On gratings, the elongated hMSCs exhibited an aligned actin cytoskeleton, while on unpatterned controls, spreading cells showed a random but denser actin cytoskeleton network. Expression of cytoskeleton and FA components was also altered by the nanotopography as reflected in the mechanical properties measured by atomic force microscopy (AFM) indentation. On the rigid TCPS, hMSCs on gratings exhibited lower instantaneous and equilibrium Young's moduli and apparent viscosity. On the softer PDMS, the effects of nanotopography were not significant. However, hMSCs cultured on PDMS showed lower cell mechanical properties than those on TCPS, regardless of topography. These suggest that both nanotopography and substrate stiffness could be important in determining mechanical properties, while nanotopography may be more dominant in determining the organization of the cytoskeleton and FAs.

Making it in the Modern Job Market: A Study of Communication among the Deaf and Hard of Hearing Population

Gemstone Team AUDIO (Assessing and Understanding Deaf Individuals' Occupations)

Chromosomal organization of adrenergic receptor genes.

The adrenergic receptors (ARs) (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. We have previously assigned the genes for beta 2- and alpha 2-AR to human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids and in situ chromosomal hybridization, we have now mapped the alpha 1-AR gene to chromosome 5q32----q34, the same position as beta 2-AR, and the beta 1-AR gene to chromosome 10q24----q26, the region where alpha 2-AR is located. In mouse, both alpha 2- and beta 1-AR genes were assigned to chromosome 19, and the alpha 1-AR locus was localized to chromosome 11. Pulsed field gel electrophoresis has shown that the alpha 1- and beta 2-AR genes in humans are within 300 kilobases (kb) and the distance between the alpha 2- and beta 1-AR genes is less than 225 kb. The proximity of these two pairs of AR genes and the sequence similarity that exists among all the ARs strongly suggest that they are evolutionarily related. Moreover, they likely arose from a common ancestral receptor gene and subsequently diverged through gene duplication and chromosomal duplication to perform their distinctive roles in mediating the physiological effects of catecholamines. The AR genes thus provide a paradigm for understanding the evolution of such structurally conserved yet functionally divergent families of receptor molecules.

Nested dictionary learning for hierarchical organization of imagery and text

A tree-based dictionary learning model is developed for joint analysis of imagery and associated text. The dictionary learning may be applied directly to the imagery from patches, or to general feature vectors extracted from patches or superpixels (using any existing method for image feature extraction). Each image is associated with a path through the tree (from root to a leaf), and each of the multiple patches in a given image is associated with one node in that path. Nodes near the tree root are shared between multiple paths, representing image characteristics that are common among different types of images. Moving toward the leaves, nodes become specialized, representing details in image classes. If available, words (text) are also jointly modeled, with a path-dependent probability over words. The tree structure is inferred via a nested Dirichlet process, and a retrospective stick-breaking sampler is used to infer the tree depth and width.

Imaging Learned Song Representations in Populations of Sensorimotor Neurons Essential to Vocal Communication

Perceiving or producing complex vocalizations such as speech and birdsongs require the coordinated activity of neuronal populations, and these activity patterns can vary over space and time. How learned communication signals are represented by populations of sensorimotor neurons essential to vocal perception and production remains poorly understood. Using a combination of two-photon calcium imaging, intracellular electrophysiological recording and retrograde tracing methods in anesthetized adult male zebra finches (Taeniopygia guttata), I addressed how the bird's own song and its component syllables are represented by the spatiotemporal patterns of activity of two spatially intermingled populations of projection neurons (PNs) in HVC, a sensorimotor area required for song perception and production. These experiments revealed that neighboring PNs can respond at markedly different times to song playback and that different syllables activate spatially intermingled HVC PNs within a small region. Moreover, noise correlation analysis reveals enhanced functional connectivity between PNs that respond most strongly to the same syllable and also provides evidence of a spatial gradient of functional connectivity specific to PNs that project to song motor nucleus (i.e. HVC_RA cells). These findings support a model in which syllabic and temporal features of song are represented by spatially intermingled PNs functionally organized into cell- and syllable-type networks.

Reconstruction of gross avian genome structure, organization and evolution suggests that the chicken lineage most closely resembles the dinosaur avian ancestor.

BACKGROUND: The availability of multiple avian genome sequence assemblies greatly improves our ability to define overall genome organization and reconstruct evolutionary changes. In birds, this has previously been impeded by a near intractable karyotype and relied almost exclusively on comparative molecular cytogenetics of only the largest chromosomes. Here, novel whole genome sequence information from 21 avian genome sequences (most newly assembled) made available on an interactive browser (Evolution Highway) was analyzed. RESULTS: Focusing on the six best-assembled genomes allowed us to assemble a putative karyotype of the dinosaur ancestor for each chromosome. Reconstructing evolutionary events that led to each species' genome organization, we determined that the fastest rate of change occurred in the zebra finch and budgerigar, consistent with rapid speciation events in the Passeriformes and Psittaciformes. Intra- and interchromosomal changes were explained most parsimoniously by a series of inversions and translocations respectively, with breakpoint reuse being commonplace. Analyzing chicken and zebra finch, we found little evidence to support the hypothesis of an association of evolutionary breakpoint regions with recombination hotspots but some evidence to support the hypothesis that microchromosomes largely represent conserved blocks of synteny in the majority of the 21 species analyzed. All but one species showed the expected number of microchromosomal rearrangements predicted by the haploid chromosome count. Ostrich, however, appeared to retain an overall karyotype structure of 2n=80 despite undergoing a large number (26) of hitherto un-described interchromosomal changes. CONCLUSIONS: Results suggest that mechanisms exist to preserve a static overall avian karyotype/genomic structure, including the microchromosomes, with widespread interchromosomal change occurring rarely (e.g., in ostrich and budgerigar lineages). Of the species analyzed, the chicken lineage appeared to have undergone the fewest changes compared to the dinosaur ancestor.

Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome integrity are linked to telomere function.

The short arms of the ten acrocentric human chromosomes share several repetitive DNAs, including ribosomal RNA genes (rDNA). The rDNA arrays correspond to nucleolar organizing regions that coalesce each cell cycle to form the nucleolus. Telomere disruption by expressing a mutant version of telomere binding protein TRF2 (dnTRF2) causes non-random acrocentric fusions, as well as large-scale nucleolar defects. The mechanisms responsible for acrocentric chromosome sensitivity to dysfunctional telomeres are unclear. In this study, we show that TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal changes occur. We used the controllable dnTRF2 system to precisely dissect the timing and progression of nucleolar and chromosomal instability induced by telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage and morphological changes that occur at acrocentric short arms. The rDNA repeat arrays on the short arms decondense, and are coated by RNA polymerase I transcription binding factor UBF, physically linking acrocentrics to one another as they become fusogenic. These results highlight the importance of telomere function in nucleolar stability and structural integrity of acrocentric chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to cause DNA damage at chromosome ends, but our findings suggest that it also disrupts chromosome structure beyond the telomere region, specifically within the rDNA arrays located on acrocentric chromosomes. These results have relevance for Robertsonian translocation formation in humans and mechanisms by which acrocentric-acrocentric fusions are promoted by DNA damage and repair.

Two versions of life: emotionally negative and positive life events have different roles in the organization of life story and identity.

Over 2,000 adults in their sixties completed the Centrality of Event Scale (CES) for the traumatic or negative event that now troubled them the most and for their most positive life event, as well as measures of current PTSD symptoms, depression, well-being, and personality. Consistent with the notion of a positivity bias in old age, the positive events were judged to be markedly more central to life story and identity than were the negative events. The centrality of positive events was unrelated to measures of PTSD symptoms and emotional distress, whereas the centrality of the negative event showed clear positive correlations with these measures. The centrality of the positive events increased with increasing time since the events, whereas the centrality of the negative events decreased. The life distribution of the positive events showed a marked peak in young adulthood whereas the life distribution for the negative events peaked at the participants' present age. The positive events were mostly events from the cultural life script-that is, culturally shared representations of the timing of major transitional events. Overall, our findings show that positive and negative autobiographical events relate markedly differently to life story and identity. Positive events become central to life story and identity primarily through their correspondence with cultural norms. Negative events become central through mechanisms associated with emotional distress.

A location-based communication platform: integrating file sharing with interpersonal contact

Gemstone Team FLIP (File Lending in Proximity)

The effect of collagen organization on tensile strength loss in anterior cruciate ligament grafts post-reconstruction surgery

Gemstone Team LEGS

Splintered memories or vivid landmarks? Qualities and organization of traumatic memories with and without PTSD

One hundred and eighty-one students answered a standardized questionnaire on Post-Traumatic Stress Disorder (PTSD): 25 reported trauma(s) and indicated a pattern of after-effects that matched a PTSD symptom profile, whereas 88 indicated trauma(s) but no PTSD symptom profile. Both groups answered a questionnaire addressing the recollective quality, integration and coherence of the traumatic memory that currently affected them most. Participants with a PTSD symptom profile reported more vivid recollection of emotion and sensory impressions. They reported more observer perspective in the memory (seeing themselves 'from the outside'), but no more fragmentation. They also agreed more with the statement that the trauma had become part of their identity, and perceived more thematic connections between the trauma and current events in their lives. The two groups showed different patterns of correlations which indicated different coping styles. Overall, the findings suggest that traumas form dysfunctional reference points for the organization of other personal memories in people with PTSD symptoms, leading to fluctuations between vivid intrusions and avoidance. Copyright © 2003 John Wiley & Sons, Ltd.

Considering the role of social dynamics and positional behavior in gestural communication research.

While the hominin fossil record cannot inform us on either the presence or extent of social and cognitive abilities that may have paved the way for the emergence of language, studying non-vocal communication among our closest living relatives, the African apes, may provide valuable information about how language originated. Although much has been learned from gestural signaling in non-human primates, we have not yet established how and why gestural repertoires vary across species, what factors influence this variation, and how knowledge of these differences can contribute to an understanding of gestural signaling's contribution to language evolution. In this paper, we review arguments surrounding the theory that language evolved from gestural signaling and suggest some important factors to consider when conducting comparative studies of gestural communication among African apes. Specifically, we propose that social dynamics and positional behavior are critical components that shape the frequency and nature of gestural signaling across species and we argue that an understanding of these factors could shed light on how gestural communication may have been the basis of human language. We outline predictions for the influence of these factors on the frequencies and types of gestures used across the African apes and highlight the importance of including these factors in future gestural communication research with primates.

Patient-provider communication, self-reported medication adherence, and race in a postmyocardial infarction population.

OBJECTIVES: Our objectives were to: 1) describe patient-reported communication with their provider and explore differences in perceptions of racially diverse adherent versus nonadherent patients; and 2) examine whether the association between unanswered questions and patient-reported medication nonadherence varied as a function of patients' race. METHODS: We conducted a cross-sectional analysis of baseline in-person survey data from a trial designed to improve postmyocardial infarction management of cardiovascular disease risk factors. RESULTS: Overall, 298 patients (74%) reported never leaving their doctor's office with unanswered questions. Among those who were adherent and nonadherent with their medications, 183 (79%) and 115 (67%) patients, respectively, never left their doctor's office with unanswered questions. In multivariable logistic regression, although the simple effects of the interaction term were different for patients of nonminority race (odds ratio [OR]: 2.16; 95% confidence interval [CI]: 1.19-3.92) and those of minority race (OR: 1.19; 95% CI: 0.54-2.66), the overall interaction effect was not statistically significant (P=0.24). CONCLUSION: The quality of patient-provider communication is critical for cardiovascular disease medication adherence. In this study, however, having unanswered questions did not impact medication adherence differently as a function of patients' race. Nevertheless, there were racial differences in medication adherence that may need to be addressed to ensure optimal adherence and health outcomes. Effort should be made to provide training opportunities for both patients and their providers to ensure strong communication skills and to address potential differences in medication adherence in patients of diverse backgrounds.