Intermediate phase, network demixing, boson and floppy modes, and compositional trends in glass transition temperatures of binary AsxS1-x system

The structure of binary As_xS_{1-x} glasses is elucidated using modulated-DSC, Raman scattering, IR reflectance and molar volume experiments over a wide range (8%<x<41%) of compositions. We observe a reversibility window in the calorimetric experiments, which permits fixing the three elastic phases; flexible at x<22.5%, intermediate phase (IP) in the 22.5%<x<29.5% range, and stressed-rigid at x>29.5%. Raman scattering supported by first principles cluster calculations reveal existence of both pyramidal (PYR, As(S1/2)3) and quasi-tetrahedral(QT, S=As(S1/2)3) local structures. The QT unit concentrations show a global maximum in the IP, while the concentration of PYR units becomes comparable to those of QT units in the phase, suggesting that both these local structures contribute to the width of the IP. The IP centroid in the sulfides is significantly shifted to lower As content x than in corresponding selenides, a feature identified with excess chalcogen partially segregating from the backbone in the sulfides, but forming part of the backbone in selenides. These ideas are corroborated by the proportionately larger free volumes of sulfides than selenides, and the absence of chemical bond strength scaling of Tgs between As-sulfides and As-selenides. Low-frequency Raman modes increase in scattering strength linearly as As content x of glasses decreases from x = 20% to 8%, with a slope that is close to the floppy mode fraction in flexible glasses predicted by rigidity theory. These results show that floppy modes contribute to the excess vibrations observed at low frequency. In the intermediate and stressed rigid elastic phases low-frequency Raman modes persist and are identified as boson modes. Some consequences of the present findings on the optoelectronic properties of these glasses is commented upon.Comment: Accepted for PR

Tobacco\u27s Minor Alkaloids: Effects on Place Conditioning and Nucleus Accumbens Dopamine Release in Adult and Adolescent Rats

Tobacco products are some of the most commonly used psychoactive drugs worldwide. Besides nicotine, alkaloids in tobacco include cotinine, myosmine, and anatabine. Scientific investigation of these constituents and their contribution to tobacco dependence is less well developed than for nicotine. The present study evaluated the nucleus accumbens dopamine-releasing properties and rewarding and/or aversive properties of nicotine (0.2-0.8 mg/kg), cotinine (0.5-5.0 mg/kg), anatabine (0.5-5.0 mg/kg), and myosmine (5.0-20.0 mg/kg) through in vivo microdialysis and place conditioning, respectively, in adult and adolescent male rats. Nicotine increased dopamine release at both ages, and anatabine and myosmine increased dopamine release in adults, but not adolescents. The dopamine release results were not related to place conditioning, as nicotine and cotinine had no effect on place conditioning, whereas anatabine and myosmine produced aversion in both ages. While the nucleus accumbens shell is hypothesized to play a role in strengthening drug-context associations following initiation of drug use, it may have little involvement in the motivational effects of tobacco constituents once these associations have been acquired. Effects of myosmine and anatabine on dopamine release may require a fully developed dopamine system, since no effects of these tobacco alkaloids were observed during adolescence. In summary, while anatabine and myosmine-induced dopamine release in nucleus accumbens may play a role in tobacco dependence in adults, the nature of that role remains to be elucidated

Development of an abbreviated form of the Penn Line Orientation Test using large samples and computerized adaptive test simulation.

Visuospatial processing is a commonly assessed neurocognitive domain, with deficits linked to dysfunction in right posterior regions of the brain. With the growth of large-scale clinical research studies there is an increased need for efficient and scalable assessments of neurocognition, including visuospatial processing. The purpose of the current study was to use a novel method that combines item response theory (IRT) and computerized adaptive testing (CAT) approaches to create an abbreviated form of the computerized Penn Line Orientation Test (PLOT). The 24-item PLOT was administered to 8,498 youths (aged 8 to 21) as part of the Philadelphia Neurodevelopmental Cohort study and, by web-based data collection, in an independent sample of 4,593 adults from Great Britain as part of a television documentary. IRT-based CAT simulations were used to select the best PLOT items for an abbreviated form by performing separate simulations in each group and choosing only items that were selected as useful (i.e., high item discrimination and in the appropriate difficulty range) in at least one of the simulations. Fifteen items were chosen for the final, short form of the PLOT, indicating substantial agreement among the models in how they evaluated each item's usefulness. Moreover, this abbreviated version performed comparably to the full version in tests of sensitivity to age and sex effects. This abbreviated version of the PLOT cuts administration time by 50% without detectable loss of information, which points to its feasibility for large-scale clinical and genomic studies

Digital Genome-Wide ncRNA Expression, Including SnoRNAs, across 11 Human Tissues Using PolyA-Neutral Amplification

Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available

Epidemiology of basal-like breast cancer (Breast Cancer Research and Treatment DOI: 10.1007/s10549-007-9632-6)

Risk factors for the newly identified “intrinsic” breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case–control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common subtype, exhibited risk factors typically reported for breast cancer in previous studies, including inverse associations for increased parity and younger age at first full-term pregnancy. Basal-like cases exhibited several associations that were opposite to those observed for luminal A, including increased risk for parity and younger age at first term full-term pregnancy. Longer duration breastfeeding, increasing number of children breastfed, and increasing number of months breastfeeding per child were each associated with reduced risk of basal-like breast cancer, but not luminal A. Women with multiple live births who did not breastfeed and women who used medications to suppress lactation were at increased risk of basal-like, but not luminal A, breast cancer. Elevated waist-hip ratio was associated with increased risk of luminal A in postmenopausal women, and increased risk of basal-like breast cancer in pre- and postmenopausal women. The prevalence of basal-like breast cancer was highest among premenopausal African-American women, who also showed the highest prevalence of basal-like risk factors. Among younger African-American women, we estimate that up to 68% of basal-like breast cancer could be prevented by promoting breastfeeding and reducing abdominal adiposity

A Study of the Influence of Sex on Genome Wide Methylation

Sex differences in methylation status have been observed in specific gene-disease studies and healthy methylation variation studies, but little work has been done to study the impact of sex on methylation at the genome wide locus-to-locus level or to determine methods for accounting for sex in genomic association studies. In this study we investigate the genomic sex effect on saliva DNA methylation of 197 subjects (54 females) using 20,493 CpG sites. Three methods, two-sample T-test, principle component analysis and independent component analysis, all successfully identify sex influences. The results show that sex not only influences the methylation of genes in the X chromosome but also in autosomes. 580 autosomal sites show strong differences between males and females. They are found to be highly involved in eight functional groups, including DNA transcription, RNA splicing, membrane, etc. Equally important is that we identify some methylation sites associated with not only sex, but also other phenotypes (age, smoking and drinking level, and cancer). Verification was done through an independent blood cell DNA methylation data (1298 CpG sites from a cancer panel array). The same genomic site-specific influence pattern and potential confounding effects with cancer were observed. The overlapping rate of identified sex affected genes between saliva and blood cell is 81% for X chromosome, and 8% for autosomes. Therefore, correction for sex is necessary. We propose a simple correction method based on independent component analysis, which is a data driven method and accommodates sample differences. Comparison before and after the correction suggests that the method is able to effectively remove the potentially confounding effects of sex, and leave other phenotypes untouched. As such, our method is able to disentangle the sex influence on a genome wide level, and paves the way to achieve more accurate association analyses in genome wide methylation studies

Control of Mitochondrial Morphology Through Differential Interactions of Mitochondrial Fusion and Fission Proteins

Mitochondria in mammals are organized into tubular networks that undergo frequent shape change. Mitochondrial fission and fusion are the main components mediating the mitochondrial shape change. Perturbation of the fission/fusion balance is associated with many disease conditions. However, underlying mechanisms of the fission/fusion balance are not well understood. Mitochondrial fission in mammals requires the dynamin-like protein DLP1/Drp1 that is recruited to the mitochondrial surface, possibly through the membrane-anchored protein Fis1 or Mff. Additional dynamin-related GTPases, mitofusin (Mfn) and OPA1, are associated with the outer and inner mitochondrial membranes, respectively, and mediate fusion of the respective membranes. In this study, we found that two heptad-repeat regions (HR1 and HR2) of Mfn2 interact with each other, and that Mfn2 also interacts with the fission protein DLP1. The association of the two heptad-repeats of Mfn2 is fusion inhibitory whereas a positive role of the Mfn2/DLP1 interaction in mitochondrial fusion is suggested. Our results imply that the differential binding of Mfn2-HR1 to HR2 and DLP1 regulates mitochondrial fusion and that DLP1 may act as a regulatory factor for efficient execution of both fusion and fission of mitochondria

The mediating role of shared flow and perceived emotional synchrony on compassion for others in a mindful-dancing program

While there is a growing understanding of the relationship between mindfulness and compassion, this largely relates to the form of mindfulness employed in first-generation mindfulness-based interventions such as Mindfulness-Based Stress Reduction. Consequently, there is limited knowledge of the relationship between mindfulness and compassion in respect of the type of mindfulness employed in second-generation mindfulness-based interventions (SG-MBIs), including those that employ the principle of working harmoniously as a “secular sangha.” Understanding this relationship is important because research indicates that perceived emotional synchrony (PES) and shared flow—that often arise during participation in harmonized group contemplative activities—can enhance outcomes relating to compassion, subjective well-being, and group identity fusion. This pilot study analyzed the effects of participation in a mindful-dancing SG-MBI on compassion and investigated the mediating role of shared flow and PES. A total of 130 participants were enrolled into the study that followed a quasi-experimental design with an intervention and control group. Results confirmed the salutary effect of participating in a collective mindful-dancing program, and demonstrated that shared flow and PES fully meditated the effects of collective mindfulness on the kindness and common humanity dimensions of compassion. Further research is warranted to explore whether collective mindfulness approaches, such as mindful dancing, may be a means of enhancing compassion and subjective well-being outcomes due to the mediating role of PES and shared flow.N/

DU Undergraduate Showcase: Research, Scholarship, and Creative Works: Abstracts

Abstracts from the DU Undergraduate Showcase

Disease Gene Characterization through Large-Scale Co-Expression Analysis

In the post genome era, a major goal of biology is the identification of specific roles for individual genes. We report a new genomic tool for gene characterization, the UCLA Gene Expression Tool (UGET).Celsius, the largest co-normalized microarray dataset of Affymetrix based gene expression, was used to calculate the correlation between all possible gene pairs on all platforms, and generate stored indexes in a web searchable format. The size of Celsius makes UGET a powerful gene characterization tool. Using a small seed list of known cartilage-selective genes, UGET extended the list of known genes by identifying 32 new highly cartilage-selective genes. Of these, 7 of 10 tested were validated by qPCR including the novel cartilage-specific genes SDK2 and FLJ41170. In addition, we retrospectively tested UGET and other gene expression based prioritization tools to identify disease-causing genes within known linkage intervals. We first demonstrated this utility with UGET using genetically heterogeneous disorders such as Joubert syndrome, microcephaly, neuropsychiatric disorders and type 2 limb girdle muscular dystrophy (LGMD2) and then compared UGET to other gene expression based prioritization programs which use small but discrete and well annotated datasets. Finally, we observed a significantly higher gene correlation shared between genes in disease networks associated with similar complex or Mendelian disorders.UGET is an invaluable resource for a geneticist that permits the rapid inclusion of expression criteria from one to hundreds of genes in genomic intervals linked to disease. By using thousands of arrays UGET annotates and prioritizes genes better than other tools especially with rare tissue disorders or complex multi-tissue biological processes. This information can be critical in prioritization of candidate genes for sequence analysis