Psychosocial mediators of dietary change among Hispanic/Latina breast cancer survivors in a culturally tailored dietary intervention.

OBJECTIVE: To examine psychosocial mediators of the effect of a culturally tailored dietary intervention on dietary change among Hispanic/Latina breast cancer survivors. METHODS: Hispanic/Latina breast cancer survivors (n = 70) were randomized to receive either a 12-week theory-based and culturally tailored dietary change program (intervention group, n = 34), or standard-of-care printed recommendations (control group, n = 36) (ClinicalTrials.gov NCT01414062). Fruit/vegetable intake (F/V), % calories from fat, and hypothesized psychosocial mediators were assessed at baseline, 6 and 12 months. Analysis of covariance assessed intervention effects on psychosocial mediators at 6 and 12 months. Mediation analysis using the bootstrap method evaluated the indirect intervention effects on dietary intake at 6 and 12 months through changes in psychosocial mediators at 6 and 12 months. RESULTS: Compared with controls, at 6 and 12 months, the intervention group reported greater improvements in stages of change (P < .001, P < .001, respectively), self-efficacy (P = .009, P = .002, respectively), snack preference for F/snack preference for F/V (P = .045, P = .002, respectively); at 12 months, the intervention group reported a decrease in chance-oriented external locus of control (P = .02). At 6 months, mediation analysis showed that the intervention effect was associated with an increase of 1.0 (95% CI, -0.1-2.4) serving/day of F/V, compared with the control group, although no indirect effect through the hypothesized psychosocial mediators was observed. At 12 months, the intervention was associated with an increase in 0.5 serving/day F/V through improved taste/snack preference for F/V at 6 and 12 months (95% CIs, 0.1-1.3, 0.0-1.4, respectively). CONCLUSIONS: Future programs can target improving taste/snack preference for F/V to promote dietary change in Hispanic/Latina breast cancer survivors.

Autoinhibition of Mint1 adaptor protein regulates amyloid precursor protein binding and processing.

Mint adaptor proteins bind to the amyloid precursor protein (APP) and regulate APP processing associated with Alzheimer's disease; however, the molecular mechanisms underlying Mint regulation in APP binding and processing remain unclear. Biochemical, biophysical, and cellular experiments now show that the Mint1 phosphotyrosine binding (PTB) domain that binds to APP is intramolecularly inhibited by the adjacent C-terminal linker region. The crystal structure of a C-terminally extended Mint1 PTB fragment reveals that the linker region forms a short α-helix that folds back onto the PTB domain and sterically hinders APP binding. This intramolecular interaction is disrupted by mutation of Tyr633 within the Mint1 autoinhibitory helix leading to enhanced APP binding and ß-amyloid production. Our findings suggest that an autoinhibitory mechanism in Mint1 is important for regulating APP processing and may provide novel therapies for Alzheimer's disease.

Contextualizing engineering leadership development in Science, Technology, Engineering and Mathematics.

Science, Technology, Engineering and Mathematics (STEM) disciplines recognize the need for leadership development, but the lack of a professionally endorsed model has led to a patchwork of programmes across the nation, each with its unique brand of skills development. Leadership programmes in six diverse STEM fields are included.

The cystic fibrosis-causing mutation deltaF508 affects multiple steps in cystic fibrosis transmembrane conductance regulator biogenesis.

The deletion of phenylalanine 508 in the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator is directly associated with >90% of cystic fibrosis cases. This mutant protein fails to traffic out of the endoplasmic reticulum and is subsequently degraded by the proteasome. The effects of this mutation may be partially reversed by the application of exogenous osmolytes, expression at low temperature, and the introduction of second site suppressor mutations. However, the specific steps of folding and assembly of full-length cystic fibrosis transmembrane conductance regulator (CFTR) directly altered by the disease-causing mutation are unclear. To elucidate the effects of the ΔF508 mutation, on various steps in CFTR folding, a series of misfolding and suppressor mutations in the nucleotide binding and transmembrane domains were evaluated for effects on the folding and maturation of the protein. The results indicate that the isolated NBD1 responds to both the ΔF508 mutation and intradomain suppressors of this mutation. In addition, identification of a novel second site suppressor of the defect within the second transmembrane domain suggests that ΔF508 also effects interdomain interactions critical for later steps in the biosynthesis of CFTR.

Long-term Diet and Biomarker Changes after a Short-term Intervention among Hispanic Breast Cancer Survivors: The ¡Cocinar Para Su Salud! Randomized Controlled Trial.

BACKGROUND: Among Hispanic breast cancer survivors, we examined the long-term effects of a short-term culturally based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat, and changing biomarkers associated with breast cancer recurrence risk. METHODS: Spanish-speaking women (n = 70) with a history of stage 0-III breast cancer who completed treatment were randomized to ¡Cocinar Para Su Salud! (n = 34), a culturally based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n = 36, written dietary recommendations for breast cancer survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months. We report changes between groups at 12 months in dietary intake and biomarkers using 2-sample Wilcoxon t tests and generalized estimating equation (GEE) models. RESULTS: At 12 months, the intervention group compared with the control group reported higher increases in mean daily F/V servings (total: +2.0 vs. -0.4; P < 0.01), and nonsignificant decreases in the percentage of calories from fat (-2.2% vs. -1.1%; P = 0.69) and weight (-2.6 kg vs. -1.5 kg; P = 0.56). Compared with controls, participants in the intervention group had higher increases in plasma lutein (+20.4% vs. -11.5%; P < 0.01), and borderline significant increases in global DNA methylation (+0.8% vs. -0.5%; P = 0.06). CONCLUSIONS: The short-term ¡Cocinar Para Su Salud! program was effective at increasing long-term F/V intake in Hispanic breast cancer survivors and changed biomarkers associated with breast cancer recurrence risk. IMPACT: It is possible for short-term behavioral interventions to have long-term effects on behaviors and biomarkers in minority cancer patient populations. Results can inform future study designs. Cancer Epidemiol Biomarkers Prev; 25(11); 1491-502. ©2016 AACR.

Temperature dependence of the thermodynamics of helix-coil transition.

The temperature-induced helix to coil transition in a series of host peptides was monitored using circular dichroism spectroscopy (CD) and differential scanning calorimetry (DSC). Combination of these two techniques allowed direct determination of the enthalpy of helix-coil transition for the studied peptides. It was found that the enthalpy of the helix-coil transition differs for different peptides and this difference is related to the difference in the temperature for the midpoint of helix-coil transition. The enthalpy of the helix-coil transition decreases with the increase in temperature, thus providing the first experimental estimate for the heat capacity changes upon helix-coil transition, DeltaC(p). The values for DeltaC(p) of helix-coil transition are found to be negative, which is in contrast to the positive DeltaC(p) for protein unfolding. Analysis suggests that this negative DeltaC(p) of helix-coil transition is due to the exposure of the polar peptide backbone to solvent upon helix unfolding.

Role of HdeA in acid resistance and virulence in Brucella abortus 2308.

Two-dimensional gel electrophoretic analysis of cell lysates suggests that stationary phase production of wild-type levels of an ortholog of the low pH dependent chaperone HdeA in Brucella abortus 2308 during growth in a minimal medium requires the presence of the RNA binding protein Hfq. Although mutational analysis demonstrated that HdeA contributes to acid resistance in this bacterium, this protein is not required for wild-type virulence in the BALB/c mouse model. These experimental findings indicate that the brucellae rely upon additional gene products to resist the acidic conditions they encounter in the phagosomal compartment of host macrophages.

¡Cocinar Para Su Salud!: Randomized Controlled Trial of a Culturally Based Dietary Intervention among Hispanic Breast Cancer Survivors.

BACKGROUND: There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors. OBJECTIVE: Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors. DESIGN: Participants were randomized to Intervention and Control groups. Diet recalls, detailed interviews, fasting blood, and anthropometric measures were collected at baseline, 3, 6, and 12 months. PARTICIPANTS/SETTING: Hispanic women (n=70) with stage 0 to III breast cancer who completed adjuvant treatment and lived in New York City were randomized between April 2011 and March 2012. INTERVENTION: The Intervention group (n=34) participated in ¡Cocinar Para Su Salud!, a culturally based nine-session (24 hours over 12 weeks) intervention including nutrition education, cooking classes, and food-shopping field trips. The Control group (n=36) received written dietary recommendations for breast cancer survivors. MAIN OUTCOME MEASURES: Change at 6 months in daily F/V servings and percent calories from total fat were the main outcome measures. STATISTICAL ANALYSES: Linear regression models adjusted for stratification factors and estimated marginal means were used to compare changes in diet from baseline to 3 and 6 months. RESULTS: Baseline characteristics were the following: mean age 56.6 years (standard deviation 9.7 years), mean time since diagnosis 3.4 years (standard deviation 2.7 years), mean body mass index (calculated as kg/m²) 30.9 (standard deviation 6.0), 62.9% with annual household income ≤$15,000, mean daily servings of all F/V was 5.3 (targeted F/V 3.7 servings excluding legumes/juices/starchy vegetables/fried foods), and 27.7% of daily calories from fat. More than 60% in the Intervention group attended seven or more of nine classes, with overall study retention of 87% retention at 6 months. At month 6, the Intervention group compared with Control group reported an increase in mean servings of F/V from baseline (all F/V: +2.0 vs -0.1; P=0.005; targeted F/V: +2.7 vs +0.5; P=0.002) and a nonsignificant decrease in percent calories from fat (-7.5% vs -4.4%; P=0.23) and weight (-2.5 kg vs +3.8 kg; P=0.22). CONCLUSIONS: ¡Cocinar Para Su Salud! was effective at increasing short-term F/V intake in a diverse population of Hispanic breast cancer survivors.

¡Cocinar Para Su Salud!: Randomized Controlled Trial of a Culturally Based Dietary Intervention among Hispanic Breast Cancer Survivors.

BACKGROUND: There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors. OBJECTIVE: Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors. DESIGN: Participants were randomized to Intervention and Control groups. Diet recalls, detailed interviews, fasting blood, and anthropometric measures were collected at baseline, 3, 6, and 12 months. PARTICIPANTS/SETTING: Hispanic women (n=70) with stage 0 to III breast cancer who completed adjuvant treatment and lived in New York City were randomized between April 2011 and March 2012. INTERVENTION: The Intervention group (n=34) participated in ¡Cocinar Para Su Salud!, a culturally based nine-session (24 hours over 12 weeks) intervention including nutrition education, cooking classes, and food-shopping field trips. The Control group (n=36) received written dietary recommendations for breast cancer survivors. MAIN OUTCOME MEASURES: Change at 6 months in daily F/V servings and percent calories from total fat were the main outcome measures. STATISTICAL ANALYSES: Linear regression models adjusted for stratification factors and estimated marginal means were used to compare changes in diet from baseline to 3 and 6 months. RESULTS: Baseline characteristics were the following: mean age 56.6 years (standard deviation 9.7 years), mean time since diagnosis 3.4 years (standard deviation 2.7 years), mean body mass index (calculated as kg/m(2)) 30.9 (standard deviation 6.0), 62.9% with annual household income ≤$15,000, mean daily servings of all F/V was 5.3 (targeted F/V 3.7 servings excluding legumes/juices/starchy vegetables/fried foods), and 27.7% of daily calories from fat. More than 60% in the Intervention group attended seven or more of nine classes, with overall study retention of 87% retention at 6 months. At month 6, the Intervention group compared with Control group reported an increase in mean servings of F/V from baseline (all F/V: +2.0 vs -0.1; P=0.005; targeted F/V: +2.7 vs +0.5; P=0.002) and a nonsignificant decrease in percent calories from fat (-7.5% vs -4.4%; P=0.23) and weight (-2.5 kg vs +3.8 kg; P=0.22). CONCLUSIONS: ¡Cocinar Para Su Salud! was effective at increasing short-term F/V intake in a diverse population of Hispanic breast cancer survivors.

Noncharged amino acid residues at the solvent-exposed positions in the middle and at the C terminus of the alpha-helix have the same helical propensity.

It was established previously that helical propensities of different amino acid residues in the middle of alpha-helix in peptides and in proteins are very similar. The statistical analysis of the protein helices from the known three-dimensional structures shows no difference in the frequency of noncharged residues in the middle and at the C terminus. Yet, experimental studies show distinctive differences for the helical propensities of noncharged residues in the middle and in the C terminus in model peptides. Is this a general effect, and is it applicable to protein helices or is it specific to the model alanine-based peptides? To answer this question, the effects of substitutions at positions 28 (middle residue) and 32 (C2 position at the C terminus) of the alpha-helix of ubiquitin on the stability of this protein are measured by using differential scanning calorimetry. The two data sets produce similar values for intrinsic helix propensity, leading to a conclusion that noncharged amino acid residues at the solvent-exposed positions in the middle and at the C terminus of the alpha-helix have the same helical propensity. This conclusion is further supported with an excellent correlation between the helix propensity scale obtained for the two positions in ubiquitin with the experimental helix propensity scale established previously and with the statistical distribution of the residues in protein helices.

Decoy receptor 3 (DcR3) is proteolytically processed to a metabolic fragment having differential activities against Fas ligand and LIGHT.

Fas ligand (FasL) and Fas receptor are members of the tumor necrosis factor (TNF) receptor and ligand family that play an important role in regulating apoptosis in normal physiology. Decoy receptor 3 (DcR3) is a novel member of the TNF receptor superfamily, which binds to and blocks the activities of the ligands FasL and LIGHT. We have demonstrated that DcR3 was degraded rapidly to a major circulating metabolic fragment after subcutaneous administration in primates and mice. This fragment was also generated in subcutaneous tissue homogenate in vitro. Mass spectrometry and N-terminal sequencing indicated that DcR3 was proteolytically cleaved between R218 and A219 in the primary sequence to yield the fragment DcR3(1-218). While retaining its ability to bind LIGHT and inhibit LIGHT-mediated activities, DcR3(1-218) no longer bound FasL and did not inhibit FasL-mediated apoptosis in vitro. The primary sequence of DcR3 was molecularly engineered, changing the arginine residue at position 218 to glutamine to generate an analog, DcR3(R218Q), which we termed FLINT (LY498919). We demonstrated that FLINT was more stable to proteolytic degradation in vitro and in vivo and maintained its activity against both soluble FasL and soluble LIGHT in vitro. As a result, the modification in the sequence of DcR3 to produce FLINT (LY498919) should result in a pharmacologically superior molecule in the therapeutic intervention of diseases in which the pathogenesis is linked to FasL-mediated apoptotic or inflammatory events.

Residential relocation by older adults in response to incident cardiovascular health events: a case-crossover analysis.

OBJECTIVE: We use a case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new home address. METHODS: We conducted an ambidirectional case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new address using data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults from four U.S. sites beginning in 1989. Relocation was assessed twice a year during follow-up. Event occurrences were classified as present or absent for the period preceding the first reported move, as compared with an equal length of time immediately prior to and following this period. RESULTS: Older adults (65+) that experience incident cardiovascular disease had an increased probability of reporting a change of residence during the following year (OR 1.6, 95% confidence interval (CI) = 1.2-2.1). Clinical conditions associated with relocation included stroke (OR: 2.0, 95% CI: 1.2-3.3), angina (OR: 1.6, 95% CI: 1.0-2.6), and congestive heart failure (OR: 1.5, 95% CI: 1.0-2.1). CONCLUSIONS: Major incident cardiovascular disease may increase the probability of residential relocation in older adults. Case-crossover analyses represent an opportunity to investigate triggering events, but finer temporal resolution would be crucial for future research on residential relocations.

Using microbial genome annotation as a foundation for collaborative student research.

We used the Integrated Microbial Genomes Annotation Collaboration Toolkit as a framework to incorporate microbial genomics research into a microbiology and biochemistry course in a way that promoted student learning of bioinformatics and research skills and emphasized teamwork and collaboration as evidenced through multiple assessment mechanisms. Student teams in microbiology used bioinformatics tools to identify and characterize gene products from Mucilaginibacter paludis necessary for the synthesis of specific amino acids and then designed and carried out growth experiments to determine if the organism could indeed synthesize the amino acids. Students in biochemistry worked to characterize one of the amino acid biosynthetic pathways reconstructed by a previous microbiology class through amplification and cloning of the M. paludis genes and complementation analysis of Escherichia coli mutants.

Enthalpy of helix-coil transition: missing link in rationalizing the thermodynamics of helix-forming propensities of the amino acid residues.

It is known that different amino acid residues have effects on the thermodynamic stability of an alpha-helix. The underlying mechanism for the thermodynamic helical propensity is not well understood. The major accepted hypothesis is the difference in the side-chain configurational entropy loss upon helix formation. However, the changes in the side-chain configurational entropy explain only part of the thermodynamic helical propensity, thus implying that there must be a difference in the enthalpy of helix-coil transition for different residues. This work provides an experimental test to this hypothesis. Direct calorimetric measurements of folding of a model host peptide in which the helix formation is induced by metal binding is applied to a wide range of residue types, both naturally occurring and nonnatural, at the guest site. Based on the calorimetric results for 12 peptides, it was found that indeed there is a difference in the enthalpy of helix-coil transition for different amino acid residues, and simple empirical rules that define these differences are presented. The obtained difference in the enthalpies of helix-coil transition complement the differences in configurational entropies and provide the complete thermodynamic characterization of the helix-forming tendencies.

The Brucella abortus Cu,Zn superoxide dismutase is required for optimal resistance to oxidative killing by murine macrophages and wild-type virulence in experimentally infected mice.

Two-dimensional gel electrophoretic analysis of cell lysates from Brucella abortus 2308 and the isogenic hfq mutant Hfq3 revealed that the RNA binding protein Hfq (also known as host factor I or HF-I) is required for the optimal stationary phase production of the periplasmic Cu,Zn superoxide dismutase SodC. An isogenic sodC mutant, designated MEK2, was constructed from B. abortus 2308 by gene replacement, and the sodC mutant exhibited much greater susceptibility to killing by O(2)(-) generated by pyrogallol and the xanthine oxidase reaction than the parental 2308 strain supporting a role for SodC in protecting this bacterium from O(2)(-) of exogenous origin. The B. abortus sodC mutant was also found to be much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and the attenuation displayed by MEK2 in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon (IFN-gamma). The attenuation displayed by the B. abortus sodC mutant in both resting and IFN-gamma-activated macrophages was alleviated, however, when these host cells were treated with the NADPH oxidase inhibitor apocynin. Consistent with its increased susceptibility to killing by cultured murine macrophages, the B. abortus sodC mutant also displayed significant attenuation in experimentally infected C57BL6J mice compared to the parental strain. These experimental findings indicate that SodC protects B. abortus 2308 from the respiratory burst of host macrophages. They also suggest that reduced SodC levels may contribute to the attenuation displayed by the B. abortus hfq mutant Hfq3 in the mouse model.

Brucella stationary-phase gene expression and virulence.

The capacity of the Brucella spp. to establish and maintain long-term residence in the phagosomal compartment of host macrophages is critical to their ability to produce chronic infections in their mammalian hosts. The RNA binding protein host factor I (HF-I) encoded by the hfq gene is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B. melitensis counterpart in experimentally infected animals indicate that stationary-phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages. The nature of the Brucella HF-I-regulated genes that have been identified to date suggests that the corresponding gene products contribute to the remarkable capacity of the brucellae to resist the harsh environmental conditions they encounter during their prolonged residence in the phagosomal compartment.