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BackgroundIsobutanol is considered a potential biofuel, thanks to its high-energy content and octane value, limited water solubility, and compatibility with gasoline. As its biosynthesis pathway is known, a microorganism, such as Saccharomyces cerevisiae, that inherently produces isobutanol, can serve as a good engineering host. Isobutanol's toxicity, however, is a major obstacle for bioproduction. This study is to understand how yeast tolerates isobutanol.ResultsA S. cerevisiae gene-deletion library with 5006 mutants was used to screen genes related to isobutanol tolerance. Image recognition was efficiently used for high-throughput screening via colony size on solid media. In enrichment analysis of the 161 isobutanol-sensitive clones identified, more genes than expected were mapped to tryptophan biosynthesis, ubiquitination, and the pentose phosphate pathway (PPP). Interestingly, adding exogenous tryptophan enabled both tryptophan biosynthesis and PPP mutant strains to overcome the stress. In transcriptomic analysis, cluster analysis of differentially expressed genes revealed the relationship between tryptophan and isobutanol stress through some specific cellular functions, such as biosynthesis and transportation of amino acids, PPP, tryptophan metabolism, nicotinate/nicotinamide metabolism (e.g., nicotinamide adenine dinucleotide biosynthesis), and fatty acid metabolism.ConclusionsThe importance of tryptophan in yeast's tolerance to isobutanol was confirmed by the recovery of isobutanol tolerance in defective strains by adding exogenous tryptophan to the growth medium. Transcriptomic analysis showed that amino acid biosynthesis- and transportation-related genes in a tryptophan biosynthesis-defective host were up-regulated under conditions similar to nitrogen starvation. This may explain why ubiquitination was required for the protein turnover. PPP metabolites may serve as precursors and cofactors in tryptophan biosynthesis to enhance isobutanol tolerance. Furthermore, the tolerance mechanism may also be linked to tryptophan downstream metabolism, including the kynurenine pathway and nicotinamide adenine dinucleotide biosynthesis. Both pathways are responsible for cellular redox balance and anti-oxidative ability. Our study highlights the central role of tryptophan in yeast's isobutanol tolerance and offers new clues for engineering a yeast host with strong isobutanol tolerance.

Objectives: This paper explores parent coaching experiences supporting parents of young children newly diagnosed with type 1 diabetes in a clinical trial. Methods: In a trial for 157 parents, those in the intervention arm (n = 116) were paired with a parent coach (n = 37; Mage = 37.9 years, SD = 3.9; 94.6% mothers, 81.1% White non-Hispanic). Parent coaches provided diabetes-specific social support. Parent coaches completed monthly surveys and satisfaction/feasibility surveys, with a subset (n = 7) undergoing qualitative interviews at the end of this study. Results: There were 2262 contacts between participants and their parent coaches, averaging 14.4 (SD = 9.3) per participant. Parent coaches reported that the most commonly used methods were text messages (67.9%) and emails (18.7%), with 33.6% having in-person visits. Coaches reported high satisfaction and belief in their usefulness to participants during the first 9 months after T1D diagnosis. Themes discussed by parent coaches about their experience in mentoring included relationship building, expertise sharing, personal growth, gratification, and intervention optimization suggestions. Conclusions: Parent coaching post T1D diagnosis involves regular, multi-method contacts. It is highly acceptable and valuable for parent coaches to mentor other parents of young children newly diagnosed with T1D. [ABSTRACT FROM AUTHOR]

Background: Given parents' elevated stress following children's diagnoses of type I diabetes (T1D), more information about protective factors is needed. The current study examined social support from various sources (e.g., partner, family, general) in relation to stress among mothers and fathers of young children shortly following T1D diagnosis. Methods: Participants included 157 children ages 1-6 recently diagnosed with T1D and their parents (152 mothers and 59 fathers) who were enrolled in a behavioral randomized controlled trial (RCT). Mothers and fathers self-reported on their demographic background, social support and stress; T1D data were parent report and/or gathered from medical records. Results: Maternal and paternal stress were examined in two separate regression models. Higher general social support predicted less stress for both mothers and fathers. For mothers, higher family support predicted less stress, while college educations status predicted more stress. For fathers, more partner support predicted less stress. Discussion: Findings contribute to the literature on gender differences in source-specific social support and psychosocial functioning in a pediatric health population. Sample characteristics limit generalizability of results, and future studies should aim to include diverse samples. Results have both scientific and clinical implications for supporting families following T1D diagnosis. Public Significance Statement Different psychosocial approaches may be needed to support mothers and fathers during their children's initial Tl D diagnoses. Keywords: T1D, parent stress, social support, Type I diabetes (T1D) diagnoses in young children have significantly increased in recent years (Streisand & Monaghan, 2014). The T1D medical regimen is complex, requiring frequent monitoring of blood glucose [...]

For older adolescents and young adults (AYAs) with type 1 diabetes, successful transition from pediatric to adult diabetes care requires ongoing planning and support. Yet, the transition to adult care is not always smooth. Some AYAs struggle to leave pediatric care or experience significant gaps between pediatric and adult diabetes care. The use of diabetes-specific transition readiness assessments can inform transition planning and support successful preparation for adult care. This study evaluated transition readiness in a diverse sample of AYAs nearing transition to adult diabetes care. Findings suggest that AYAs may benefit from additional preparation and education related to sexual health, tobacco use, and diabetes complications. [ABSTRACT FROM AUTHOR]

Objective: Despite the emotional challenges of parental adjustment to a child's type 1 diabetes diagnosis and the unique complexities of early childhood, there are few programs designed to meet the needs of parents of young children at new onset. This study evaluated First STEPS (Study of Type 1 in Early childhood and Parenting Support), a stepped-care behavioral intervention designed to support parents' psychosocial functioning and promote children's glycemic outcomes.Research Design and Methods: Using a two-site randomized clinical trial design, parents (n = 157) of children aged 1-6 years completed baseline data within 2 months of diabetes diagnosis and were randomly assigned to intervention (n = 115) or usual care (n = 42) for 9 months. Intervention steps included: 1) peer parent coaching, with step-ups to 2) structured behavioral counseling and 3) professional consultations with a diabetes educator and psychologist, based on parent mood and child HbA1c. Participants completed follow-ups at 9 and 15 months postrandomization. Primary outcomes were parent depressive symptoms and child HbA1c.Results: Depressive symptoms improved in both groups, and intervention parents had significantly lower depressive symptoms at the 9- and 15-month follow-ups compared with usual care. HbA1c decreased in both groups, but there were no between-group differences at 9 or 15 months.Conclusions: First STEPS improved parents' mood following young children's type 1 diabetes diagnosis. Results indicate likely benefits of parent coach support, supplemented by intervention intensifications, including behavioral intervention and diabetes education. This model has high potential for patient engagement. The absence of a medical intervention component may explain null findings for HbA1c; incorporating targeted behavioral support for intensive diabetes treatment may maximize intervention impact. [ABSTRACT FROM AUTHOR]

Background: Children classified as behaviorally inhibited (BI) are at risk for social anxiety. Risk for anxiety is moderated by both parental behavior and social–emotional competence. Grounded in developmental–transactional theory, the Turtle Program involves both parent and child treatment components delivered within the peer context. Our pilot work demonstrated beneficial effects of the Turtle Program ('Turtle') over a waitlist control group. Herein, we report results of a rigorous randomized controlled trial (RCT) comparing Turtle to the best available treatment for young children high in BI, Cool Little Kids (CLK). Methods: One hundred and fifty‐one parents and their 3.5‐ to 5‐year‐old children selected on the basis of BI were randomly assigned to Turtle or CLK, delivered in group format over 8 weeks. Effects on child anxiety, life interference, BI, and observed parenting were examined at post‐treatment and 1‐year follow‐up. ClinicalTrials.gov registration: NCT02308826. Results: No significant main effect differences were found between Turtle and CLK on child anxiety; children in both programs evidenced significant improvements in BI, anxiety severity, family accommodation, and child impairment. However, Turtle yielded increased observed warm/engaged parenting and decreased observed negative control, compared with CLK. Parental social anxiety moderated effects; parents with higher anxiety demonstrated diminished improvements in child impairment, and parent accommodation in CLK, but not in Turtle. Children of parents with higher anxiety demonstrated more improvements in child BI in Turtle, but not in CLK. Conclusions: Turtle and CLK are both effective early interventions for young children with BI. Turtle is more effective in improving parenting behaviors associated with the development and maintenance of child anxiety. Turtle also proved to be more effective than CLK for parents with social anxiety. Results suggest that Turtle should be recommended when parents have social anxiety; however, in the absence of parent anxiety, CLK may offer a more efficient treatment model. [ABSTRACT FROM AUTHOR]

Abstract Background To achieve an economical cellulosic ethanol production, a host that can do both cellulosic saccharification and ethanol fermentation is desirable. However, to engineer a non-cellulolytic yeast to be such a host requires synthetic biology techniques to transform multiple enzyme genes into its genome. Results A technique, named Promoter-based Gene Assembly and Simultaneous Overexpression (PGASO), that employs overlapping oligonucleotides for recombinatorial assembly of gene cassettes with individual promoters, was developed. PGASO was applied to engineer Kluyveromycesmarxianus KY3, which is a thermo- and toxin-tolerant yeast. We obtained a recombinant strain, called KR5, that is capable of simultaneously expressing exoglucanase and endoglucanase (both of Trichodermareesei), a beta-glucosidase (from a cow rumen fungus), a neomycin phosphotransferase, and a green fluorescent protein. High transformation efficiency and accuracy were achieved as ~63% of the transformants was confirmed to be correct. KR5 can utilize beta-glycan, cellobiose or CMC as the sole carbon source for growth and can directly convert cellobiose and beta-glycan to ethanol. Conclusions This study provides the first example of multi-gene assembly in a single step in a yeast species other than Saccharomyces cerevisiae. We successfully engineered a yeast host with a five-gene cassette assembly and the new host is capable of co-expressing three types of cellulase genes. Our study shows that PGASO is an efficient tool for simultaneous expression of multiple enzymes in the kefir yeast KY3 and that KY3 can serve as a host for developing synthetic biology tools.

Objective: To examine recurrence and timing of maternal depression as predictors of depressive and conduct symptoms in children with and without ADHD. Method: Children aged 4 to 6 years (125 ADHD, 122 comparison) were followed over 8 years. Maternal depression was assessed annually. Youth depressive and conduct symptoms were assessed at ages 12 to 14. Results: Recurrence of maternal depression predicted youth depressive and conduct symptoms at ages 12 to 14; child ADHD moderated relations between recurrence of maternal depression and youth depressive (but not conduct) symptoms. Early adolescent exposure to maternal depression predicted age 12 to 14 depressive symptoms for all children. Exposure to maternal depression during early childhood, childhood, and early adolescence each independently predicted youth conduct symptoms. Conclusion: Recurrence and timing of maternal depression predict comorbid symptoms in early adolescents, particularly for youth with ADHD. Findings inform the prevention of comorbidities in children with ADHD where maternal depression is present. (J. of Att. Dis. XXXX; XX(X) XX-XX). [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CW, BB, and FC declare no conflicts of interest. BM has investigator-initiated funding from Tandem Diabetes Care, Inc., and Dexcom. MM is currently employed by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (NIDDK/NIH). All data for this manuscript were collected prior to her employment at NIDDK/NIH.