vProtein: Identifying Optimal Amino Acid Complements from Plant-Based Foods

Background: Indispensible amino acids (IAAs) are used by the body in different proportions. Most animal-based foods provide these IAAs in roughly the needed proportions, but many plant-based foods provide different proportions of IAAs. To explore how these plant-based foods can be better used in human nutrition, we have created the computational tool vProtein to identify optimal food complements to satisfy human protein needs. Methods: vProtein uses 1251 plant-based foods listed in the United States Department of Agriculture standard release 22 database to determine the quantity of each food or pair of foods required to satisfy human IAA needs as determined by the 2005 daily recommended intake. The quantity of food in a pair is found using a linear programming approach that minimizes total calories, total excess IAAs, or the total weight of the combination. Results: For single foods, vProtein identifies foods with particularly balanced IAA patterns such as wheat germ, quinoa, and cauliflower. vProtein also identifies foods with particularly unbalanced IAA patterns such as macadamia nuts, degermed corn products, and wakame seaweed. Although less useful alone, some unbalanced foods provide unusually good complements, such as Brazil nuts to legumes. Interestingly, vProtein finds no statistically significant bias toward grain/ legume pairings for protein complementation. These analyses suggest that pairings of plant-based foods should be based on the individual foods themselves instead of based on broader food group-food group pairings. Overall, the most efficien

Nutrient density of beverages in relation to climate impact

The food chain contributes to a substantial part of greenhouse gas (GHG) emissions and growing evidence points to the urgent need to reduce GHGs emissions worldwide. Among suggestions were proposals to alter food consumption patterns by replacing animal foods with more plant-based foods. However, the nutritional dimensions of changing consumption patterns to lower GHG emissions still remains relatively unexplored. This study is the first to estimate the composite nutrient density, expressed as percentage of Nordic Nutrition Recommendations (NNR) for 21 essential nutrients, in relation to cost in GHG emissions of the production from a life cycle perspective, expressed in grams of CO2-equivalents, using an index called the Nutrient Density to Climate Impact (NDCI) index. The NDCI index was calculated for milk, soft drink, orange juice, beer, wine, bottled carbonated water, soy drink, and oat drink. Due to low-nutrient density, the NDCI index was 0 for carbonated water, soft drink, and beer and below 0.1 for red wine and oat drink. The NDCI index was similar for orange juice (0.28) and soy drink (0.25). Due to a very high-nutrient density, the NDCI index for milk was substantially higher (0.54) than for the other beverages. Future discussion on how changes in food consumption patterns might help avert climate change need to take both GHG emission and nutrient density of foods and beverages into account

Recognition memory, self-other source memory, and theory-of-mind in children with autism spectrum disorder.

This study investigated semantic and episodic memory in autism spectrum disorder (ASD), using a task which assessed recognition and self-other source memory. Children with ASD showed undiminished recognition memory but significantly diminished source memory, relative to age- and verbal ability-matched comparison children. Both children with and without ASD showed an “enactment effect”, demonstrating significantly better recognition and source memory for self-performed actions than other-person-performed actions. Within the comparison group, theory-of-mind (ToM) task performance was significantly correlated with source memory, specifically for other-person-performed actions (after statistically controlling for verbal ability). Within the ASD group, ToM task performance was not significantly correlated with source memory (after controlling for verbal ability). Possible explanations for these relations between source memory and ToM are considered

'Everyday memory' impairments in autism spectrum disorders

‘Everyday memory’ is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Children’s Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed

Conserved Orb6 Phosphorylation Sites Are Essential for Polarized Cell Growth in Schizosaccharomyces pombe

The Ndr-related Orb6 kinase is a key regulator of polarized cell growth in fission yeast, however the mechanism of Orb6 activation is unclear. Activation of other Ndr kinases involves both autophosphorylation and phosphorylation by an upstream kinase. Previous reports suggest that the Nak1 kinase functions upstream from Orb6. Supporting this model, we show that HA-Orb6 overexpression partially restored cell polarity in nak1 ts cells. We also demonstrated by coimmunoprecipitation and in vitro binding assays that Nak1 and Orb6 physically interact, and that the Nak1 C-terminal region is required forNak1/Orb6 complex formation in vivo. However, results from in vitro kinase assays did not show phosphorylation of recombinant Orb6 by HA-Nak1, suggesting that Orb6 activation may not involve direct phosphorylation by Nak1. To investigate the role of Orb6 phosphorylation and activity, we substituted Ala at the ATP-binding and conserved phosphorylation sites. Overexpression of kinase-dead HA-Orb6K122A in wild-type cells resulted in a loss of cell polarity, suggesting that it has a dominant-negative effect, and it failed to rescue the polarity defect of nak1 or orb6 ts mutants. Recombinant GST-Orb6S291A did not autophosphorylate in vitro suggesting that Ser291 is the primary autophosphorylation site. HA-Orb6S291A overexpression only partially rescued the orb6 polarity defect and failed to rescue the nak1 defect, suggesting that autophosphorylation is important for Orb6 function. GST-Orb6T456A autophosphorylated in vitro, indicating that the conserved phosphorylation site at Thr456 is not essential for kinase activity. However, HA-Orb6T456A overexpression had similar effects as overexpressing kinase-dead HA-Orb6K122A, suggesting that Thr456 is essential for Orb6 function in vivo. Also, we found that both phosphorylation site mutations impaired the ability of Myc-Nak1 to coimmunoprecipitate with HA-Orb6. Together, our results suggest a model whereby autophosphorylation of Ser291 and phosphorylation of Thr456 by an upstream kinase promote Nak1/Orb6 complex formation and Orb6 activation

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCα), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies

The effects of phenoxodiol on the cell cycle of prostate cancer cell lines

Background: Prostate cancer is associated with a poor survival rate. The ability of cancer cells to evade apoptosis and exhibit limitless replication potential allows for progression of cancer from a benign to a metastatic phenotype. The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes. Methods: Three prostate cancer cell lines-LNCaP, DU145, and PC3 were cultured in vitro, and then treated with phenoxodiol (10 μM and 30 μM) for 24 and 48 h. The expression of cell cycle genes p21WAF1, c-Myc, Cyclin-D1, and Ki-67 was investigated by Real Time PCR. Results: Here we report that phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle, with the resultant arrest due to the upregulation of p21WAF1 in all the cell lines in response to treatment, indicating that activation of p21WAF1 and subsequent cell arrest was occurring via a p53 independent manner, with induction of cytotoxicity independent of caspase activation. We found that c-Myc and Cyclin-D1 expression was not consistently altered across all cell lines but Ki-67 signalling expression was decreased in line with the cell cycle arrest. Conclusions: Phenoxodiol demonstrates an ability in prostate cancer cells to induce significant cytotoxicity in cells by interacting with p21WAF1 and inducing cell cycle arrest irrespective of p53 status or caspase pathway interactions. These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer

Turnover rates of nitrogen stable isotopes in the salt marsh mummichog, Fundulus heteroclitus, following a laboratory diet switch

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Springer-Verlag GmbH for personal use, not for redistribution. The definitive version was published in Oecologia 147 (2006): 391-395, doi:10.1007/s00442-005-0277-z.Nitrogen stable isotopes are frequently used in ecological studies to estimate trophic position and determine movement patterns. Knowledge of tissue-specific turnover and nitrogen discrimination for the study organisms is important for accurate interpretation of isotopic data. We measured δ15 N turnover in liver and muscle tissue in juvenile mummichogs, Fundulus heteroclitus, following a laboratory diet switch. Liver tissue turned over significantly faster than muscle tissue suggesting the potential for a multiple tissue stable isotope approach to study movement and trophic position over different time scales; metabolism contributed significantly to isotopic turnover for both liver and muscle. Nitrogen diet-tissue discrimination was estimated at between 0.0 and 1.2‰ for liver and –1.0 and 0.2‰ for muscle. This is the first experiment to demonstrate a significant variation in δ15 N turnover between liver and muscle tissues in a fish species.This study was funded by NSF LTER grant OCE-9726921