Genetically encoded discovery of perfluoroaryl macrocycles that bind to albumin and exhibit extended circulation in vivo.

Peptide-based therapeutics have gained attention as promising therapeutic modalities, however, their prevalent drawback is poor circulation half-life in vivo. In this paper, we report the selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine SAr chemistry, with decafluoro-diphenylsulfone (DFS). Testing of the binding of the selected peptides to albumin identified SICRFFC as the lead sequence.

Genetically-encoded discovery of proteolytically stable bicyclic inhibitors for morphogen NODAL.

In this manuscript, we developed a two-fold symmetric linchpin () that converts readily available phage-displayed peptides libraries made of 20 common amino acids to genetically-encoded libraries of bicyclic peptides displayed on phage. combines an aldehyde-reactive group and two thiol-reactive groups; it bridges two side chains of cysteine [C] with an N-terminal aldehyde group derived from the N-terminal serine [S], yielding a novel bicyclic topology that lacks a free N-terminus. Phage display libraries of SXCXXXXXXC sequences, where X is any amino acid but Cys, were converted to a library of bicyclic -[S]X[C]XXXXXX[C] peptides in 45 ± 15% yield.

The experience of parental cancer among emerging adult university students.

Cancer is a disease that can have negative as well as some positive outcomes for the survivor, caregiver, and offspring. To date, there has been little research on the experiences of emerging adult offspring. When these offspring are also university students, they can experience unique challenges.

Undergraduate, Female, Nutrition Students' Perceptions of Curricular Influence on Attitudes toward Individuals with Obesity.

Purpose: This qualitative study, guided by a phenomenological approach, explored senior-level undergraduate, nutrition students' perceptions of how obesity and weight bias were addressed in the undergraduate curricula and how the curricula influenced their attitudes toward individuals with obesity.

Methods: Twenty senior-level undergraduate, nutrition students from the University of Guelph participated in interviews. Interviews were audio-recorded and transcribed verbatim.

Evaluation of Daily Physical Activity (DPA) policy implementation in Ontario: surveys of elementary school administrators and teachers.

Background: School-based structured opportunities for physical activity can provide health-related benefits to children and youth, and contribute to international guidelines recommending 60 min of moderate-to-vigorous physical activity (MVPA) per day. In 2005, the Ministry of Education in Ontario, Canada, released the Daily Physical Activity (DPA) policy requiring school boards to "ensure that all elementary students, including students with special needs, have a minimum of twenty minutes of sustained MVPA each school day during instructional time". This paper reports on the first provincial study evaluating implementation fidelity to the DPA policy in Ontario elementary schools and classrooms.

Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance.

Glucagon-like peptide-2 receptor agonists have therapeutic potential for the treatment of intestinal diseases. The native hGLP-2, a 33 amino acid gastrointestinal peptide, is not a suitable clinical candidate, due to its very short half-life in humans. In search of GLP-2 receptor agonists with better pharmacokinetic characteristics, a series of GLP-2 analogues containing Gly substitution at position 2, norleucine in position 10, and hydrophobic substitutions in positions 11 and/or 16 was designed and synthesized.

Lead discovery and optimization strategies for peptide macrocycles.

Peptide macrocycles represent a chemical space where the best of biological tools can synergize with the best of chemical approaches in the quest for leads against undruggable targets. Peptide macrocycles offer some key advantages in both lead discovery and lead optimization phases of drug discovery when compared to natural product and synthetic macrocycles. In addition, they are uniquely positioned to capitalize on the therapeutic potential of peptides because cyclization can help drive selectivity, potency and overcome the common limitations of metabolic instability of peptides.

Adolescents' self-efficacy to overcome barriers to Physical Activity Scale.

This paper describes a revised measure of self-efficacy to overcome barriers to moderate and vigorous physical activity in a sample of 484 high school students in Toronto, Ontario. The students had a mean age of 15.3 years.

Clustering of specific health-related behaviours among Toronto adolescents.

Purpose: The clustering of specific health-related behaviours was examined among adolescents.

Methods: In 2005, cluster analysis was conducted to identify homogeneous groups of Toronto, Ontario, 14- to 17-year-old adolescents (n=445) with similar behaviour patterns according to self-reported measures of moderate to vigorous physical activity (metabolic equivalent [MET] hours a week of MVPA), sedentary behaviours (viewing television or videos, using a computer/the internet, doing homework, and talking with friends), fruit and vegetable consumption, and alcohol consumption.

Results: Three clusters of adolescents were identified: "active, high screen-time users," "active, low screen-time users," and "less active, least frequent drinkers.

The effect of parental feeding behaviours and participation of children in organized sports/activities on child body mass index.

Purpose: In this cross-sectional descriptive study, we explored the relationship of parental feeding practices and child physical activity levels with measured body mass index (BMI) in a sample of 97 Ontario preschoolers.

Methods: Child weight and height were measured; physical activity and sedentary behaviours were assessed by questionnaire. Preschoolers' parents used the Child Feeding Questionnaire to report their attitudes, concerns, and practices in relation to child feeding.

Convergent synthesis of a helical, prehairpin HR1 trimer from HIV gp41.

A helical, prehairpin trimer covering the majority of the HR1 region of human immunodeficiency virus gp41 was achieved by chemically coupling three identical 51 amino acid peptides. A 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene pinwheel 'cap' was used to trimerize the peptides by taking advantage of the unique property of triacyl fluoride and orthogonal protection and deprotection. The resulting protein is fully helical, highly thermostable and soluble.

Challenges in assessing the implementation and effectiveness of physical activity and nutrition policy interventions as natural experiments.

The Ontario (Canada) government has instituted a policy requiring elementary schools to offer at least 20 min of daily physical activity for students in Grades 1-8 and replace non-nutritious vending machine foods with healthier choices. These policy interventions represent 'natural experiments' offering unique opportunities for conducting research and evaluation. The use of natural experiments to contribute evidence on the effectiveness of policy interventions is identified as an underused tool for public health [Tudor-Locke, C.

Impact of the enfuvirtide resistance mutation N43D and the associated baseline polymorphism E137K on peptide sensitivity and six-helix bundle structure.

Enfuvirtide (ENF), the first human immunodeficiency virus type 1 (HIV-1) fusion inhibitor approved for clinical use, acts by binding to gp41 heptad repeat 1 (HR1) and preventing its interaction with the viral HR2 region. Treatment-emergent resistance to ENF has been mapped to residues within HR1, and these mutations decrease its susceptibility to ENF and may reduce viral fitness and pathogenesis, although the mechanism for these effects is not clear. N43D, a common ENF resistance mutation, was found in in vitro assays to cause a 5-50-fold in antiviral activity.

Design of an engineered N-terminal HIV-1 gp41 trimer with enhanced stability and potency.

HIV fusion is mediated by a conformational transition in which the C-terminal region (HR2) of gp41 interacts with the N-terminal region (HR1) to form a six-helix bundle. Peptides derived from the HR1 form a well-characterized, trimeric coiled-coil bundle in the presence of HR2 peptides, but there is little structural information on the isolated HR1 trimer. Using protein design, we have designed synthetic HR1 peptides that form soluble, thermostable HR1 trimers.

Food security in older adults: community service provider perceptions of their roles.

Food insecurity in older adults is influenced by financial constraints, functional disability, and isolation. Twenty-eight social- and community-service providers participated in four focus groups to report (a) perceptions and experiences with food insecurity in their older clients, (b) beliefs about their potential role(s) in promoting food security, and (c) opinions about constraints that influenced these roles. A constant comparison analysis identified key themes.

Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus.

Enfuvirtide (ENF), the first approved fusion inhibitor (FI) for HIV, is a 36-aa peptide that acts by binding to the heptad repeat 1 (HR1) region of gp41 and preventing the interaction of the HR1 and HR2 domains, which is required for virus-cell fusion. Treatment-acquired resistance to ENF highlights the need to create FI therapeutics with activity against ENF-resistant viruses and improved durability. Using rational design, we have made a series of oligomeric HR2 peptides with increased helical structure and with exceptionally high HR1/HR2 bundle stability.

Supporting healthy eating among preschoolers: challenges for child care staff.

Purpose: The child care setting can help preschoolers develop healthy eating habits. Establishing such habits may increase preschoolers' likelihood of carrying them into adulthood, which can decrease the risk of nutrition-related chronic diseases. Challenges in supporting preschoolers' healthy eating were investigated among child care staff.

The decline in physical activity among adolescent students: a cross-national comparison.

Background: The decline in physical activity during adolescence is a key public health concern. This comparative study assesses whether the age-related decline in physical activity among high school students occurs similarly in the United States (U.S.

The relationship between vigorous physical activity and juvenile delinquency: a mediating role for self-esteem?

Many policy-related reviews of the potential social value of sport and physical activity list the prevention of juvenile delinquency. We examined the relationships among vigorous physical activity, self-esteem, and delinquent behavior among adolescents in a large cross-sectional survey of Ontario adolescents. Data are based on questionnaires from 3,796 students (range 11-20 years) derived from the 2005 Ontario Student Drug Use Survey.

The relationship between sedentary activities and physical inactivity among adolescents: results from the Canadian Community Health Survey.

Purpose: To evaluate the relationships between the time spent on sedentary activities (computer usage, video game playing, television viewing, and reading) and physical inactivity in a sample of youth (aged 12-19 years) from the 2000-2001 Canadian Community Health Survey.

Methods: The study sample included 7982 youth (4034 males, 3948 females) across Canada (mean age: 15.61 years, SD: 2.

A provincial study of opportunities for school-based physical activity in secondary schools.

Purpose: Adolescents spend considerable time at school and thus it is important to understand their opportunities for school-based physical activity. This study surveyed Ontario secondary schools to identify the range of structured opportunities and their engagement by students.

Methods: A questionnaire was mailed to key informants in 600 randomly selected secondary schools in Ontario, for which 474 respondents (79%) returned completed questionnaires.

Eat smart! Workplace Cafeteria Program evaluation of the nutrition component.

Purpose: The nutrition component of the Eat Smart! Workplace Cafeteria Program (ESWCP) in a hospital was evaluated. We assessed staff's frequency of visits to and purchases in the hospital cafeteria, attitudes about the program, short-term eating behaviour change, and suggestions to improve the ESWCP.

Methods: Questionnaires were sent to hospital staff members who were not on leave (n=504).

Adolescent girls' perceived barriers to participation in physical activity.

Research shows a decline in physical activity levels during adolescence, particularly among girls. This study explored perceived barriers to participation in moderate and vigorous physical activity among adolescent girls who live in a large ethnoracially and socioeconomically diverse city. A total of 73 adolescent girls in Toronto participated in 1 of 7 focus group sessions which were audiotaped and transcribed verbatim, and qualitative software was used to facilitate data analysis.

Empowerment evaluation in redesigning a public health unit nutrition program.

This article illustrates how empowerment evaluation was used in Toronto Public Health's (TPH) nutrition programming redesign to consult with staff about how roles, responsibilities, and organisational structure could be changed to improve how nutrition programs are delivered. One of three moderators facilitated the ten two-hour focus group sessions in TPH. TPH staff, namely 71 front-line staff and 13 managers who were responsible for providing community nutrition services, participated in the study.