Evolution and variation in amide aminoacyl-tRNA synthesis.

The amide proteogenic amino acids, asparagine and glutamine, are two of the twenty amino acids used in translation by all known life. The aminoacyl-tRNA synthetases for asparagine and glutamine, asparaginyl-tRNA synthetase and glutaminyl tRNA synthetase, evolved after the split in the last universal common ancestor of modern organisms. Before that split, life used two-step indirect pathways to synthesize asparagine and glutamine on their cognate tRNAs to form the aminoacyl-tRNA used in translation. These two-step pathways were retained throughout much of the bacterial and archaeal domains of life and eukaryotic organelles. The indirect routes use non-discriminating aminoacyl-tRNA synthetases (non-discriminating aspartyl-tRNA synthetase and non-discriminating glutamyl-tRNA synthetase) to misaminoacylate the tRNA. The misaminoacylated tRNA formed is then transamidated into the amide aminoacyl-tRNA used in protein synthesis by tRNA-dependent amidotransferases (GatCAB and GatDE). The enzymes and tRNAs involved assemble into complexes known as transamidosomes to help maintain translational fidelity. These pathways have evolved to meet the varied cellular needs across a diverse set of organisms, leading to significant variation. In certain bacteria, the indirect pathways may provide a means to adapt to cellular stress by reducing the fidelity of protein synthesis. The retention of these indirect pathways versus acquisition of asparaginyl-tRNA synthetase and glutaminyl tRNA synthetase in lineages likely involves a complex interplay of the competing uses of glutamine and asparagine beyond translation, energetic costs, co-evolution between enzymes and tRNA, and involvement in stress response that await further investigation.

Six-month intervention with wild blueberries improved speed of processing in mild cognitive decline: a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: As the sector of the population over 65y increases, cognitive decline and dementia become a public health issue. Interventions to improve brain health and thus, quality of life for older adults are needed. OBJECTIVE: It was hypothesized that those consuming a flavonoid-rich, lyophilized wild blueberry powder would evidence improvements in cognitive performance as measured behaviorally and electrophysiologically compared to those consuming a placebo powder across a 6-month intervention period. DESIGN: In a double-blind, randomized placebo-controlled trial, participants experiencing cognitive issues as determined by scores on the Montreal Cognitive Assessment (MoCA) were randomized to consume either wild blueberry (n = 44) or placebo (n = 42) powder daily for 6 months. Participants who were not experiencing any cognitive issues were included as a reference group (n = 45). Participants were tested at baseline and outcome on the Cambridge Neurological Test Automated Battery (CANTAB) and in an electrophysiological paradigm known as event-related potentials (ERP). RESULTS: Tests of specific cognitive abilities using the CANTAB showed speed of processing not only improved in the blueberry intervention group relative to the placebo group across the 6-month intervention, but blueberries also restored speed of processing to the level of the reference group. The ERP results also showed that, relative to those consuming placebo, speed of processing improved for those in the blueberry group; this improvement was most prominent in those 75-80y. CONCLUSIONS: Consumption of wild blueberries for six months improves cognitive aging sequelae by improving the speed of information processing in older adults.Trial registration: ClinicalTrials.gov identifier: NCT01515098.

Transnasal Humidified Rapid-Insufflation Ventilatory Exchange for Difficult Airway Management in Adults With Recessive Dystrophic Epidermolysis Bullosa: A Case Series.

Airway management of adult patients with recessive dystrophic epidermolysis bullosa presents significant challenges associated with tissue fragility and distortion of airway anatomy. This retrospective case series describes 11 adult patients with recessive dystrophic epidermolysis bullosa and difficult airways undergoing 24 general anesthetics in which transnasal humidified rapid-insufflation ventilatory exchange was used for preoxygenation and apneic oxygenation. Despite an average time to intubation of over 6 minutes, transnasal humidified rapid-insufflation ventilatory exchange provided oxygenation before endotracheal intubation without the need for bag-mask ventilation or supraglottic airway ventilation, facilitating smooth and atraumatic flexible scope intubation. There were no major adverse events.

Anesthetic Management of Adults With Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is a group of rare, inherited diseases characterized by skin fragility and multiorgan system involvement that presents many anesthetic challenges. Although the literature regarding anesthetic management focuses primarily on the pediatric population, as life expectancy improves, adult patients with EB are more frequently undergoing anesthesia in nonpediatric hospital settings. Safe anesthetic management of adult patients with EB requires familiarity with the complex and heterogeneous nature of this disease, especially with regard to complications that may worsen during adulthood. General, neuraxial, and regional anesthetics have all been used safely in patients with EB. A thorough preoperative evaluation is essential. Preoperative testing should be guided by EB subtype, clinical manifestations, and extracutaneous complications. Advanced planning and multidisciplinary coordination are necessary with regard to timing and operative plan. Meticulous preparation of the operating room and education of all perioperative staff members is critical. Intraoperatively, utmost care must be taken to avoid all adhesives, shear forces, and friction to the skin and mucosa. Special precautions must be taken with patient positioning, and standard anesthesia monitors must be modified. Airway management is often difficult, and progressive airway deterioration can occur in adults with EB over time. A smooth induction, emergence, and postoperative course are necessary to minimize blister formation from excess patient movement. With careful planning, preparation, and precautions, adult patients with EB can safely undergo anesthesia.

Behavioral and Cognitive Differences in Early Childhood related to Prenatal Marijuana Exposure.

Prenatal marijuana exposure (PME) negatively impacts child development and behavior; however, few studies have examined these associations at early ages among children exposed to today's highly potent marijuana. Using a prospective prenatal cohort (Columbus, Ohio, USA), PME was determined from maternal self-report, medical chart abstraction, and urine toxicology from prenatal visits and delivery. At age 3.5 years, 63 offspring children completed tasks assessing executive function (EF), visual spatial ability, emotion regulation, and aggressive behavior. Caregivers reported on children's EF and problem behaviors. Logistic regressions and analyses of covariance controlling for key variables were used to examine associations between PME and child outcomes. Compared to non-exposed children, children with PME had more sleep-related problems, withdrawal symptoms, and externalizing problems, including aggressive behaviors and oppositional defiant behaviors. Children with and without PME did not differ in terms of executive functioning. Findings suggest behavioral problems associated with PME may manifest by age 3.5.

Measuring implementation of medication optimization services: Development and validation of an implementation outcomes questionnaire.

BACKGROUND: Implementation outcomes serve as progress and success indicators of the implementation process. They are also key antecedents to achieving the more traditional clinical outcomes typically associated with a service. Despite their importance, there are few implementation outcomes measures with appropriate psychometric properties, none of which have yet been adapted for medication optimization services. OBJECTIVES: This study aims to develop and validate the Implementation Outcomes Questionnaire (IOQ) to assess implementation of medication optimization services, starting with Comprehensive Medication Management (CMM). The resulting IOQ is a 40-item self-report instrument for six implementation outcomes, including adoption, acceptability, feasibility, appropriateness, penetration, and sustainability. METHODS: A three-phase approach was used to develop and validate the IOQ. Development of the instrument, Phase I, was informed by a targeted search of existing implementation outcomes measures in other fields, a review of suitableoptions options by an expert panel, and item adaptation. To assess content validity, Phase II, an internal vetting process was conducted using an adapted version of Rubio and colleagues' methodology. Evidence of reliability and construct validity, Phase III, was obtained through a pilot test with 167 pharmacists within 78 different care settings. RESULTS: Overall, the results supported the reliability and validity (both content and construct) of the IOQ, with further psychometric testing needed for adoption. The items' relevance, clarity, and alignment with each implementation concept were high, except for Penetration. As a result, the Penetration items were refined for further use. Best-fit models were identified for each outcome based on the MCFA analyses, thereby providing insights into the factor structures and interpretation for each measure. Cronbach' alphas indicated good internal consistency. CONCLUSIONS: This questionnaire is the first of its kind tailored to medication optimization services, starting with CMM. Access to this survey should facilitate measurement of implementation outcomes, thereby increasing the likelihood of achieving the desired clinical outcomes.

Feeding Infants at the Breast or Feeding Expressed Human Milk: Long-Term Cognitive, Executive Function, and Eating Behavior Outcomes at Age 6 Years.

OBJECTIVE: To examine how expressed milk feeding diverges from feeding at the breast in its association with neurodevelopment and behavior. We hypothesized that longer and exclusive feeding at the breast only (ie, no formula, no feeding expressed milk) would be associated with the optimal cognitive developmental, executive function, and eating behaviors and that expressed milk feeding would be associated with less-optimal outcomes. STUDY DESIGN: The Moms2Moms cohort (Ohio, US) reported infant feeding practices at 12 months postpartum and children's global cognitive ability, executive function, and eating behaviors at 6 years. Linear and log-binomial regression models estimated associations with durations of feeding at the breast, expressed milk, human milk (modes combined), and formula. RESULTS: Among 285 participants, each month of exclusive feeding at the breast only was associated with a decreased risk of clinically meaningful executive function (working memory) deficit (adjusted relative risk [RR] 0.78, 95% CI 0.63-0.96) but was unassociated with inhibition (adjusted RR 0.92, 95% CI 0.85-1.01). Feeding expressed milk was not clearly related to executive function outcomes. No associations with global cognitive ability were observed. Weak associations were observed with eating behaviors for some feeding practices. CONCLUSIONS: Feeding at the breast may offer advantages to some aspects of executive function that expressed milk may not. Large, prospective studies exploring mechanisms could further distinguish the effect of feeding mode from that of nutrients.

Parental Perceptions and Behaviors Regarding Child Weight Status among Toddlers Born Preterm.

OBJECTIVE: Childhood obesity is a significant determinant of adult obesity. Among children born preterm, rapid "catch-up growth" in infancy increases the risk of later obesity. Parental perceptions of their child's weight status may compound the child's biologically heightened risk of obesity. STUDY DESIGN: We performed a secondary analysis of data on parental perceptions of child weight status from a randomized controlled trial (2012-2017, n = 331 toddlers born preterm). We used the Child Feeding Questionnaire (CFQ) to measure parental child feeding behaviors and beliefs. We calculated the prevalence of incorrect weight estimation, and used t-tests and chi-square tests to compare sample characteristics by correct versus incorrect weight estimation. We calculated odds ratios (ORs) for factors associated with parental underestimation of child weight status. RESULTS: Most (90%) children were of normal weight, whereas 3% were underweight and 7% were overweight. A majority (75%) of parents correctly estimated their child's weight status. Incorrect weight estimation was only associated with child's actual weight. Parents of overweight children were more likely to underestimate their child's weight status than parents of normal weight children (OR: 2.23, 95% confidence interval: 2.00-2.49). Mean CFQ scores differed by the child's actual weight status but not by the child's estimated weight status. CONCLUSION: Among these toddlers born preterm, significantly higher proportions of parents with underweight and overweight children incorrectly estimated their child's weight status relative to parents of normal weight children. Our findings suggest that weight underestimation could be a problem in this population, although it was not associated with changes in feeding practices.

Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

BACKGROUND: Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm. OBJECTIVES: The aim of the trial was to examine the effects of supplementing toddlers born preterm with DHA and arachidonic acid (AA) for 180 d on growth and adiposity. METHODS: Omega Tots, a randomized placebo-controlled trial, was conducted between April 2012 and March 2017. Children born at <35 wk gestation who were 10-16 mo in corrected age were assigned to receive daily oral supplements of DHA and AA (200 mg each, "DHA + AA") or corn oil (placebo) for 180 d. Prespecified secondary outcomes included weight, length, head circumference, mid-upper arm circumference, triceps and subscapular skinfolds, BMI, and their respective z scores, and body fat percentage, which were measured at baseline and trial completion. Mixed-effects regression was used to compare the change in outcomes between the DHA + AA and placebo groups, controlling for baseline values. RESULTS: Among 377 children included in the analysis (median corrected age = 15.7 mo, 48.3% female), 348 (92.3%) had growth or adiposity data at baseline and trial end. No statistically significant differences between the DHA + AA and placebo groups in growth or adiposity outcomes were observed. For instance, the change in weight-for-age z scores was 0.1 for the DHA + AA group and 0.0 for the placebo group (effect size = 0.01, P = 0.99). However, post-hoc subgroup analyses revealed a statistically significant interaction between treatment group and sex, suggesting somewhat slower linear growth for females assigned to the DHA + AA group compared with the placebo group. CONCLUSIONS: Among toddlers born preterm, daily supplementation with DHA + AA for 180 d resulted in no short-term differences in growth or adiposity compared with placebo. If DHA supplementation is implemented after the first year of life, it can be expected to have no effect on short-term growth or adiposity. This trial is registered with clinicaltrials.gov as NCT02199808.

Effect of Docosahexaenoic Acid Supplementation vs Placebo on Developmental Outcomes of Toddlers Born Preterm: A Randomized Clinical Trial.

Importance: Intake of dietary docosahexaenoic acid (DHA) among toddlers is low. Supplementation may benefit developmental outcomes of toddlers who were born preterm. Objective: To determine whether 6 months of daily DHA supplementation improves developmental outcomes of toddlers who were born preterm. Design, Setting, and Participants: A randomized, fully masked, placebo-controlled trial was conducted from April 26, 2012, to March 24, 2017, at a large US pediatric academic center with 9 neonatal intensive care units. Children born at less than 35 weeks' gestation who were 10 to 16 months corrected age underwent 6 months of intervention. Of 2363 children assessed, 982 were eligible, 605 declined, and 377 enrolled and were randomized. Analyses were according to intent to treat. Interventions: One-to-one allocation to receive daily microencapsulated DHA, 200 mg, and arachidonic acid (AA), 200 mg (DHA+AA), or microencapsulated corn oil (placebo). Main Outcomes and Measures: The primary outcome specified a priori was Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive composite score at 16 to 22 months corrected age. Secondary outcomes were Bayley-III language and motor composite scores and Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire effortful control and activity level scores. Subgroup analyses defined a priori were by income, sex, and birth weight. Results: Among 377 children randomized and included in the analysis (182 girls and 195 boys; median corrected age, 15.7 months), 338 children (89.7%) had complete data on the primary outcome. Bayley-III cognitive scores did not differ between the DHA+AA and placebo groups (difference in change, 0.5 [95% CI, -1.8 to 2.8]; effect size, 0.05; P = .66). Assignment to the DHA+AA group had a small to medium negative effect on Bayley-III language scores among children with lower birth weights (eg, a child with a birth weight of 1000 g assigned to receive DHA+AA experienced a 4.1-point relative decrease, while a child assigned to placebo did not; P = .03 for interaction). Supplementation had a similar negative effect on effortful control scores among children with annual household incomes greater than $35 000 (difference in change, -0.3 [95% CI, -0.4 to -0.1]; effect size, -0.37; P = .01). Bayley-III motor scores and activity level scores were unaffected. Conclusions and Relevance: Daily supplementation with 200 mg of DHA and 200 mg of AA for 6 months resulted in no improvement in cognitive development and early measures of executive function vs placebo, and may have resulted in negative effects on language development and effortful control in certain subgroups of children. These findings do not support DHA supplementation in the second year of life for children who are born preterm. Trial Registration: ClinicalTrials.gov Identifier: NCT01576783.

Bidirectional effects between parenting sensitivity and child behavior: A cross-lagged analysis across middle childhood and adolescence.

Using a longitudinal, cross-lagged design, this study examined the bidirectional relations between mothers' and fathers' sensitivity and children's externalizing (EXT) and internalizing (INT) behavior from middle childhood into adolescence. The subsample comprised families (N = 578) in which the mother and father cohabitated from the study's first time point (child age = 54 months) through Age 15 in the longitudinal NICHD Study of Early Child Care and Youth Development. Study results revealed differential patterns for mother-child and father-child relations in the full sample and separately for males and females. The full cross-lagged models revealed that child EXT behavior predicted maternal sensitivity, but not vice versa, and fathers' sensitivity and child behavior were reciprocally interrelated. There was a significant indirect pathway from early paternal sensitivity to later EXT in males, and from early maternal sensitivity to INT in females. The results point to the important roles that fathers play in child INT and EXT behaviors and important differences between males and females. (PsycINFO Database Record

ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers.

Background: Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives: The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods: This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results: Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions: This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.

Omega-6/omega-3 fatty acid intake of children and older adults in the U.S.: dietary intake in comparison to current dietary recommendations and the Healthy Eating Index.

BACKGROUND: Omega-6 and omega-3 fatty acids (FAs) and their ratio have been shown to affect cognitive function in children and older adults. With these analyses, we aimed to describe omega-6 and omega-3 FA intake among children and older adults in light of FA intake recommendations and with consideration of overall diet. METHODS: Data were merged from two cross-sectional studies with 219 children 7 to 12 years old and one longitudinal study with 133 adults 65 to 79 years old. Demographic data, anthropometric data, and Healthy Eating Index scores were used to study relations among the omega-6 to omega-3 FA ratio and age, education, body mass index, and diet quality. FA intake, demographic, and anthropometric data were examined using partial correlations, t-tests, and analysis of variance. RESULTS: Most children and adults consumed at least the recommended amount of alpha-linolenic acid (LNA; omega-3) for their age and gender without consuming high amounts of linoleic acid (LA; omega-6), but did not consume sufficient eicosapentaenoic acid (EPA; omega-) and docosahexaenoic acid (DHA; omega-3). The average omega-6 to omega-3 ratios in both groups were lower than previously reported. Eating lower ratios was associated with healthier diets and consuming adequate amounts of several other nutrients. No demographic or anthropometric variables were related to FA intake in children. Adults with a college degree had significantly lower ratios than those without a college degree. CONCLUSIONS: American children and older adults are able to consume more balanced omega-6 to omega-3 ratios than has been indicated by commodity data. However, very few American children met even the lowest recommendations for EPA and DHA intake. Research is needed to clarify recommendations for the optimal ratio across development, which may aid in increasing EPA and DHA intake and improving health outcomes in the United States. TRIAL REGISTRATION: ClinicalTrials.gov NCT02199808 13 July 2014, NCT01823419 (retrospectively registered) 20 March 2013, and NCT01515098 18 January 2012.

Exploring Provider Use of a Digital Implementation Support System for School Mental Health: A Pilot Study.

This pilot study explored provider use of an online system, Centervention, to support the delivery of empirically supported school-based mental health interventions (ESIs); and associations between components of this system [resources, training, technical assistance (TA), feedback loops], implementation indicators, and student outcomes. Multilevel modeling data were collected from 39 providers implementing ESIs with 758 students. Training, TA, and progress monitoring predicted ESI adherence, and perceived value of resources and TA influenced student responsiveness. Greater adherence was predictive of better socio-emotional outcomes. Interviews with 15 providers illuminated how they used these four Centervention support strategies. Implications for digital implementation support research are discussed.

Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms.

Delayed language development may be an early indicator of autism spectrum disorder (ASD). Early intervention is critical for children with ASD, and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development, a secondary trial outcome, in children at risk for ASD. We randomized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months, and measured their language abilities at baseline and after supplementation. Gesture use, but not word production, increased for children in the treatment group more than children in the placebo group. These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD.

Executive functions and the ω-6-to-ω-3 fatty acid ratio: a cross-sectional study.

BACKGROUND: The ω-6 (n-6) to ω-3 (n-3) fatty acid (FA) ratio (n-6:n-3 ratio) was previously shown to be a predictor of executive function performance in children aged 7-9 y. OBJECTIVE: We aimed to replicate and extend previous findings by exploring the role of the n-6:n-3 ratio in executive function performance. We hypothesized that there would be an interaction between n-3 and the n-6:n-3 ratio, with children with low n-3 performing best with a low ratio, and those with high n-3 performing best with a high ratio. DESIGN: Children were recruited on the basis of their consumption of n-6 and n-3 FAs. The executive function performance of 78 children aged 7-12 y was tested with the use of the Cambridge Neuropsychological Test Automated Battery and a planning task. Participants provided blood for plasma FA quantification, and the caregiver completed demographic and activity questionnaires. We investigated the role of the n-6:n-3 ratio in the entire sample and separately in children aged 7-9 y (n = 41) and 10-12 y (n = 37). RESULTS: Dietary and plasma n-6:n-3 ratio and n-3 predicted performance on working memory and planning tasks in children 7-12 y old. The interaction between dietary n-6:n-3 ratio and n-3 predicted the number of moves required to solve the most difficult planning problems in children aged 7-9 y and those aged 10-12 y, similar to results from the previous study. There was also an interaction between the plasma n-6:n-3 ratio and n-3 predicting time spent thinking through the difficult 5-move planning problems. The n-6:n-3 ratio and n-3 predicted executive function performance differently in children aged 7-9 y and in those aged 10-12 y, indicating different optimal FA balances across development. CONCLUSIONS: The n-6:n-3 ratio is an important consideration in the role of FAs in cognitive function, and the optimal balance of n-6 and n-3 FAs depends on the cognitive function and developmental period studied. This trial was registered at clinicaltrials.gov as NCT02199808.

The Bacillus subtilis and Bacillus halodurans Aspartyl-tRNA Synthetases Retain Recognition of tRNA(Asn).

Synthesis of asparaginyl-tRNA (Asn-tRNA(Asn)) in bacteria can be formed either by directly ligating Asn to tRNA(Asn) using an asparaginyl-tRNA synthetase (AsnRS) or by synthesizing Asn on the tRNA. In the latter two-step indirect pathway, a non-discriminating aspartyl-tRNA synthetase (ND-AspRS) attaches Asp to tRNA(Asn) and the amidotransferase GatCAB transamidates the Asp to Asn on the tRNA. GatCAB can be similarly used for Gln-tRNA(Gln) formation. Most bacteria are predicted to use only one route for Asn-tRNA(Asn) formation. Given that Bacillus halodurans and Bacillus subtilis encode AsnRS for Asn-tRNA(Asn) formation and Asn synthetases to synthesize Asn and GatCAB for Gln-tRNA(Gln) synthesis, their AspRS enzymes were thought to be specific for tRNA(Asp). However, we demonstrate that the AspRSs are non-discriminating and can be used with GatCAB to synthesize Asn. The results explain why B. subtilis with its Asn synthetase genes knocked out is still an Asn prototroph. Our phylogenetic analysis suggests that this may be common among Firmicutes and 30% of all bacteria. In addition, the phylogeny revealed that discrimination toward tRNA(Asp) by AspRS has evolved independently multiple times. The retention of the indirect pathway in B. subtilis and B. halodurans likely reflects the ancient link between Asn biosynthesis and its use in translation that enabled Asn to be added to the genetic code.

Synergistic Effects of Human Milk Nutrients in the Support of Infant Recognition Memory: An Observational Study.

The aim was to explore the relation of human milk lutein; choline; and docosahexaenoic acid (DHA) with recognition memory abilities of six-month-olds. Milk samples obtained three to four months postpartum were analyzed for fatty acids, lutein, and choline. At six months, participants were invited to an electrophysiology session. Recognition memory was tested with a 70-30 oddball paradigm in a high-density 128-lead event-related potential (ERP) paradigm. Complete data were available for 55 participants. Data were averaged at six groupings (Frontal Right; Frontal Central; Frontal Left; Central; Midline; and Parietal) for latency to peak, peak amplitude, and mean amplitude. Difference scores were calculated as familiar minus novel. Final regression models revealed the lutein X free choline interaction was significant for the difference in latency scores at frontal and central areas (p < 0.05 and p < 0.001; respectively). Higher choline levels with higher lutein levels were related to better recognition memory. The DHA X free choline interaction was also significant for the difference in latency scores at frontal, central, and midline areas (p < 0.01; p < 0.001; p < 0.05 respectively). Higher choline with higher DHA was related to better recognition memory. Interactions between human milk nutrients appear important in predicting infant cognition, and there may be a benefit to specific nutrient combinations.