Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.

Palmitoylation is the post-translational addition of a palmitate moiety to a cysteine residue through a covalent thioester bond. The addition and removal of this modification is controlled by both palmitoyl acyl-transferases and thioesterases. Using bioinformatic analysis, we identified 22 DHHC family palmitoyl acyl-transferase homologs in the Drosophila genome. We used in situ hybridization, RT-PCR, and published FlyAtlas microarray data to characterize the expression patterns of all 22 fly homologs. Our results indicate that all are expressed genes, but several, including CG1407, CG4676, CG5620, CG6017/dHIP14, CG6618, CG6627, and CG17257 appear to be enriched in neural tissues suggesting that they are important for neural function. Furthermore, we have found that several may be expressed in a sex-specific manner with adult male-specific expression of CG4483 and CG17195. Using tagged versions of the DHHC genes, we demonstrate that fly DHHC proteins are primarily located in either the Golgi Apparatus or Endoplasmic Reticulum in S2 cells, except for CG1407, which was found on the plasma membrane. We also characterized the subcellular localization and expression of the three known thioesterases: Palmitoyl-protein Thioesterase 1 (Ppt1), Palmitoyl-protein Thioesterase 2 (Ppt2), and Acyl-protein Thioesterase 1 (APT1). Our results indicate that Ppt1 and Ppt2 are the major lysosomal thioesterases while APT1 is the likely cytoplasmic thioesterase. Finally, in vivo rescue experiments show that Ppt2 expression cannot rescue the neural inclusion phenotypes associated with loss of Ppt1, further supporting distinct functions and substrates for these two thioesterases. These results will serve as the basis for a more complete understanding of the protein palmitoylome's normal cellular functions in the fly and will lead to further insights into the molecular etiology of diseases associated with the mis-regulation of palmitoylation.

Objective: To create supportive environments to reduce sugary drink consumption and increase water consumption by partnering with remote Aboriginal and Torres Strait Islander communities in Cape York. Methods: This paper applied qualitative and quantitative methods to evaluate a co‐designed multi‐strategy health promotion initiative, implemented over 12 months from 2017 to 2018. Outcome measures included changes in community readiness, awareness of the social marketing campaign and changes in drink availability. Changes in store drink sales were measured in one community and compared to sales in a control store. Results: Community readiness to address sugary drink consumption increased in two of the three communities. Awareness of social marketing campaign messaging was high (56–94%). Availability of drinking water increased in all communities. Water sales as a proportion of total drink volume sales increased by 3.1% (p<0.001) while sugary drink volume sales decreased by 3.4% (p<0.001). Conclusions: A multi‐component strategy with strong engagement from local government, community leaders and the wider community was associated with positive changes in community readiness, drink availability and sales. Implications for public health: Partnering with community leaders in the co‐design of strategies to create environments that support healthy drink consumption can stimulate local action and may positively affect drink consumption.

The inherent strength of individual carbon nanotubes (CNTs) offers considerable opportunity for the development of advanced, lightweight composite structures. Recent work in the fabrication and application of CNT forms such as yarns and sheets has addressed early nanocomposite limitations with respect to nanotube dispersion and loading and has pushed the technology toward structural composite applications. However, the high tensile strength of an individual CNT has not directly translated into that of sheets and yarns, where the bulk material strength is limited by intertube electrostatic attractions and slippage. The focus of this work was to assess postprocessing of CNT sheets and yarns to improve the macro-scale strength of these material forms. Both small-molecule functionalization and electron-beam irradiation were evaluated as means to enhance the tensile strength and Young's modulus of the bulk CNT materials. Mechanical testing revealed a 57% increase in tensile strength of CNT sheets upon functionalization compared with unfunctionalized sheets, while an additional 48% increase in tensile strength was observed when functionalized sheets were irradiated. Similarly, small-molecule functionalization increased tensile strength of yarn by up to 25%, whereas irradiation of the functionalized yarns pushed the tensile strength to 88% beyond that of the baseline yarn.

No abstract

Infantile-onset Neuronal Ceroid Lipofuscinosis (INCL) is a severe pediatric neurodegenerative disorder produced by mutations in the gene encoding palmitoyl-protein thioesterase 1 (Ppt1). This enzyme is responsible for the removal of a palmitate post-translational modification from an unknown set of substrate proteins. To better understand the function of Ppt1 in neurons, we performed an unbiased dominant loss-of-function genetic modifier screen in Drosophila using a previously characterized Ppt1 gain-of-function system. The enhancers and suppressors identified in our screen make novel connections between Ppt1 and genes involved in cellular trafficking and the modulation of synaptic growth. We further support the relevance of our screen by demonstrating that Garland cells from Ppt1 loss-of-function mutants have defects in endocytic trafficking. Endocytic tracer uptake and ultrastructural analysis of these non-neuronal cells points to Ppt1 playing a role in modulating the early stages of vesicle formation. This work lays the groundwork for further experimental exploration of these processes to better understand their contributions to the INCL disease process.

We studied implicit relational learning by embedding contextual relational information into a multiple-object tracking task. In two experiments, participants were instructed to track two or four out of eight moving objects and report at the end of the trial whether a single cued object was among those they tracked (yes/no task). The stimulus display also contained two background strips of different width. In the informative condition, the location of the cued object predicted the correct choice: If the answer was "yes", then the cued object was always located next to the narrower strip; otherwise, it was always located next to the wider strip (or vice versa). In the random condition, the location of the object did not predict the correct choice. Participants in the informative condition consistently displayed lower tracking accuracy than in the random condition, possibly due to attentional demands introduced by implicit relational task. At the same time, participants in the informative condition demonstrated no awareness of the task structure; instead, their reports were consistent with the attempts to track moving objects. Our task can provide a suitable model for studying implicit relational learning in adult participants that is essential for establishing generality of factors affecting relational learning.

Carbon nanotube (CNT) sheets represent a novel implementation of CNTs that enable the tailoring of electrical and mechanical properties for applications in the automotive and aerospace industries. Small molecule functionalization and postprocessing techniques, such as irradiation with high-energy particles, are methods that can enhance the mechanical properties of CNTs. However, the effect that these modifications have on the electrical conduction mechanisms has not been extensively explored. By characterizing the mechanical and electrical properties of multiwalled carbon nanotube (MWCNT) sheets with different functional groups and irradiation doses, we can expand our insights into the extent of the trade-off that exists between mechanical strength and electrical conductivity for commercially available CNT sheets. Such insights allow for the optimization of design pathways for engineering applications that require a balance of material property enhancements.