Further Astrochemical Insights From Bond Strengths of Small Molecules Containing Atoms From the First Three Rows of the Periodic Table

The atoms contributing to the strongest “single bonds” on the periodic table do not continue to produce the strongest “double bonds” or “triple bonds.” In fact, the opposite appears to be the case. This quantum chemical examination of nominal X = Y and X ≡ Y bonds in model molecules of atoms from the first three rows of the periodic table shows that the strongest “double bond” is in formaldehyde once the astrophysically-depleted Be and B atoms are removed from consideration. The strongest “triple bond” is a close match between acetylene and N2. However, these results indicate that astrophysical regions containing a high abundance of hydride species will likely be areas where inorganic oxide formation is favored. Those where H2 molecules have already been dissociated will favor organic/volatile astrochemistry

Discovery of Thienoquinolone Derivatives as Selective and ATP Non-Competitive CDK5/p25 Inhibitors by Structure-Based Virtual Screening

Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer’s disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2-c]quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP non-competitive CDK5/p25 inhibitors with good CDK2/E selectivity

Validated determination of NRG1 Ig-like domain structure by mass spectrometry coupled with computational modeling

High resolution hydroxyl radical protein footprinting (HR-HRPF) is a mass spectrometry-based method that measures the solvent exposure of multiple amino acids in a single experiment, offering constraints for experimentally informed computational modeling. HR-HRPF-based modeling has previously been used to accurately model the structure of proteins of known structure, but the technique has never been used to determine the structure of a protein of unknown structure. Here, we present the use of HR-HRPF-based modeling to determine the structure of the Ig-like domain of NRG1, a protein with no close homolog of known structure. Independent determination of the protein structure by both HR-HRPF-based modeling and heteronuclear NMR was carried out, with results compared only after both processes were complete. The HR-HRPF-based model was highly similar to the lowest energy NMR model, with a backbone RMSD of 1.6 Å. To our knowledge, this is the first use of HR-HRPF-based modeling to determine a previously uncharacterized protein structure

Perceived crime and traffic safety is related to physical activity among adults in Nigeria

Background: Neighborhood safety is inconsistently related to physical activity, but is seldom studied in developing countries. This study examined associations between perceived neighborhood safety and physical activity among Nigerian adults. Methods: In a cross-sectional study, accelerometer-based physical activity (MVPA), reported walking, perceived crime and traffic safety were measured in 219 Nigerian adults. Logistic regression analysis was conducted, and the odds ratio for meeting health guidelines for MVPA and walking was calculated in relation to four safety variables, after adjustment for potential confounders. Results: Sufficient MVPA was related to more perception of safety from traffic to walk (OR = 2.28, CI = 1.13-6.25) and more safety from crime at night (OR = 1.68, CI = 1.07-3.64), but with less perception of safety from crime during the day to walk (OR = 0.34, CI = 0.06- 0.91). More crime safety during the day and night were associated with more walking. Conclusions: Perceived safety from crime and traffic were associated with physical activity among Nigerian adults. These findings provide preliminary evidence on the need to provide safe traffic and crime environments that will make it easier and more likely for African adults to be physically active

Efficacy of a referral and physical activity program for survivors of prostate cancer [ENGAGE]: Rationale and design for a cluster randomised controlled trial

Background: Despite evidence that physical activity improves the health and well-being of prostate cancer survivors, many men do not engage in sufficient levels of activity. The primary aim of this study (ENGAGE) is to determine the efficacy of a referral and physical activity program among survivors of prostate cancer, in terms of increasing participation in physical activity. Secondary aims are to determine the effects of the physical activity program on psychological well-being, quality of life and objective physical functioning. The influence of individual and environmental mediators on participation in physical activity will also be determined.Methods/Design: This study is a cluster randomised controlled trial. Clinicians of prostate cancer survivors will be randomised into either the intervention or control condition. Clinicians in the intervention condition will refer eligible patients (n = 110) to participate in an exercise program, comprising 12 weeks of supervised exercise sessions and unsupervised physical activity. Clinicians allocated to the control condition will provide usual care to eligible patients (n = 110), which does not involve the recommendation of the physical activity program. Participants will be assessed at baseline, 12 weeks, 6 months, and 12 months on physical activity, quality of life, anxiety, depression, self-efficacy, outcome expectations, goals, and socio-structural factors.Discussion: The findings of this study have implications for clinicians and patients with different cancer types or other chronic health conditions. It will contribute to our understanding on the potential impact of clinicians promoting physical activity to patients and the long term health benefits of participating in physical activity programs.<br /

Physical activity and nutrition program for seniors (PANS): protocol of a randomized controlled trial

Background Along with reduced levels of physical activity, older Australian's mean energy consumption has increased. Now over 60% of older Australians are considered overweight or obese. This study aims to confirm if a low-cost, accessible physical activity and nutrition program can improve levels of physical activity and diet of insufficiently active 60-70 year-olds. Methods/Design This 12-month home-based randomised controlled trial (RCT) will consist of a nutrition and physical activity intervention for insufficiently active people aged 60 to 70 years from low to medium socio-economic areas. Six-hundred participants will be recruited from the Australian Federal Electoral Role and randomly assigned to the intervention (n = 300) and control (n = 300) groups. The study is based on the Social Cognitive Theory and Precede-Proceed Model, incorporating voluntary cooperation and self-efficacy. The intervention includes a specially designed booklet that provides participants with information and encourages dietary and physical activity goal setting. The booklet will be supported by an exercise chart, calendar, bi-monthly newsletters, resistance bands and pedometers, along with phone and email contact. Data will be collected over three time points: pre-intervention, immediately post-intervention and 6-months post-study. Discussion This trial will provide valuable information for community-based strategies to improve older adults' physical activity and dietary intake. The project will provide guidelines for appropriate sample recruitment, and the development, implementation and evaluation of a minimal intervention program, as well as information on minimising barriers to participation in similar programs

The adaptation of the Affective Norms for English Words (ANEW) for European Portuguese

This study presents the adaptation of the Affective Norms for English Words (ANEW; Bradley & Lang, 1999a) for European Portuguese (EP). The EP adaptation of the ANEW was based on the affective ratings made by 958 college students who were EP native speakers. Participants assessed about 60 words by considering the affective dimensions of valence, arousal, and dominance, using the Self-Assessment Manikin (SAM) in either a paper-and-pencil and a web survey procedures. Results of the adaptation of the ANEW for EP are presented. Furthermore, the differences between EP, American (Bradley & Lang, 1999a), and Spanish (Redondo, Fraga, Padrón, & Comesaña, 2007) standardizations were explored. Results showed that the ANEW words were understood in a similar way by EP, American, and Spanish subjects, although some sex and cross-cultural differences were observed. The EP adaptation of the ANEW is shown to be a valid and useful tool that will allow researchers to control and/or manipulate the affective properties of stimuli as well as to develop cross-linguistic studies. The normative values of EP adaptation of the ANEW can be downloaded at http://brm.psychonomic-journals.org/content/supplemental.COMPETE - Programa Operacional Factores de CompetitividadeFundo Europeu de Desenvolvimento Regional - FEDERQuadro de Referência Estratégico Nacional - QRENFundação para a Ciência e a Tecnologia (FCT) - research project “Procura Palavras (P-Pal ): A software program for deriving objective and subjective psycholinguistic indices for European Portuguese words

Integrative DNA Methylation and Gene Expression Analyses Identify DNA Packaging and Epigenetic Regulatory Genes Associated with Low Motility Sperm

In previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for associations with sperm function. (NCBI 1788). There was a trend among altered expression of these epigenetic regulatory genes and RPMM DNA methylation class.Using integrative genome-wide approaches we identified CpG methylation profiles and mRNA alterations associated with low sperm motility

Brand Suicide? Memory and Liking of Negative Brand Names

Negative brand names are surprisingly common in the marketplace (e.g., Poison perfume; Hell pizza, and Monster energy drink), yet their effects on consumer behavior are currently unknown. Three studies investigated the effects of negative brand name valence on brand name memory and liking of a branded product. Study 1 demonstrates that relative to nonnegative brand names, negative brand names and their associated logos are better recognised. Studies 2 and 3 demonstrate that negative valence of a brand name tends to have a detrimental influence on product evaluation with evaluations worsening as negative valence increases. However, evaluation is also dependent on brand name arousal, with high arousal brand names resulting in more positive evaluations, such that moderately negative brand names are equally as attractive as some non-negative brand names. Study 3 shows evidence for affective habituation, whereby the effects of negative valence reduce with repeated exposures to some classes of negative brand name