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Background: Multidomain interventions which incorporate exercise and dietary supplementation to target both cognitive and physical health domains may be an important approach to delay cognitive decline. Objective: The Protein Omega-3 aNd vitamin D Exercise Research (PONDER) study investigated the effects of a 6-month multifaceted intervention in community-dwelling older adults with subjective memory impairment on cognition (primary outcome), physical function, and body composition with a further 6-month follow up for cognition (secondary outcomes). Methods: Single-center, community-based, parallel-group, randomized, double-blind placebo-controlled trial involving a 6-month multifaceted intervention with a further follow-up at 12 months. A total of 147 participants [mean age 70.2 years (SD 6.1), 70% female] were randomized to a multimodal exercise program consisting of twice-weekly supervised resistance and aerobic training, combined with a daily omega-3 (900 mg EPA, 600 mg DHA), vitamin D (1000 IU) and protein (20 g) supplement (n = 73), or a control condition (n = 74) comprising stretching/flexibility sessions combined with a placebo. The primary outcome was a composite CogState measure and Trail-Making Test B-A. Results: There were no significant between-group differences in the change of cognition at 6 or 12 months or physical function outcomes at 6 months, but the intervention significantly improved total lean mass compared to controls [0.72 kg (95% CI 0.26–1.19), p = 0.001]. Conclusion: A multi-faceted intervention including an omega-3, vitamin D and protein-enriched supplement with twice-weekly exercise training did not provide any benefits to cognitive or physical function in older adults with subjective memory impairment, despite improvements in lean mass.

We examined the effect of a dietary seaweed extract—sulfated xylorhamnoglucuronan (SXRG84)—on individuals with inflammatory skin conditions. A subgroup analysis of a larger trial was undertaken, where 44 participants with skin conditions were enrolled in a double-blind placebo-controlled crossover design. Subjects ingested either SXRG84 extract (2 g/day) for six weeks and placebo for six weeks, or vice versa. At baseline, six- and twelve-weeks inflammatory markers and the gut microbiota were assessed, as well as skin assessments using the dermatology quality of life index (DQLI), psoriasis area severity index (PASI) and visual analogue scales (VAS). There were significant differences at weeks six and twelve for pro-inflammatory cytokines IFN-γ (p = 0.041), IL-1β (p = 0.030), TNF-α (p = 0.008) and the anti-inflammatory cytokine IL-10 (p = 0.026), determined by ANCOVA. These cytokines were all significantly higher at six weeks post placebo compared to twelve weeks post placebo followed by SXRG84 treatment. A total of 23% of participants reported skin improvements, as measured by VAS (mean difference 3.1, p = 0.0005) and the DQLI score (mean difference -2.0, p = 0.049), compared to the ‘non-responders’. Thus, the ingestion of SXRG84 for 6 weeks reduced inflammatory cytokines, and a subset of participants saw improvements.

BACKGROUND: The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake.PURPOSE: To evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters.METHODS: In a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements.RESULTS: Main differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, pCONCLUSIONS: This study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.

An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode species Caenorhabditis briggsae (Cbr) and Caenorhabditis elegans (Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs within Cbr DCC recruitment sites that are highly enriched on X: 13 bp MEX and 30 bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated binding in vivo. Hence, DCC binding to Cbr recruitment sites appears additive. In contrast, DCC binding to Cel recruitment sites is synergistic: mutating even one motif in vivo eliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstrated in vivo and in vitro. A single nucleotide position in Cbr MEX can determine whether Cel DCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with the conservation of target specificity for X-chromosome dosage compensation across Drosophila species and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.

Background: Gestational diabetes mellitus (GDM) affects approximately one in six pregnancies, causing a significant burden on maternal and infant health. Lifestyle interventions are first-line therapies to manage blood glucose levels (BGLs) and prevent future cardiometabolic complications. However, women with GDM experience considerable barriers to lifestyle interventions; thus, the aim of this study was to determine how women with GDM manage their condition and to identify the primary supports and barriers to lifestyle intervention participation. Methods: An online cross-sectional survey of women in Australia with a history of GDM was conducted. Questions included participant demographics, strategies used to manage BGLs, physical activity and dietary habits, and barriers and supports to lifestyle interventions. Results: A total of 665 individuals consented and responded to the advertisement, of which 564 were eligible and provided partial or complete responses to the survey questions. Most respondents were between 35 and 39 years of age (35.5%), not pregnant (75.4%), working part-time (26.7%), university-educated (58.0%), and had only one child (40.1%). Most respondents managed their BGLs through diet (88.3%), with “low-carbohydrate” diets being the most popular (72.3%), and 46.2% of respondents were undertaking insulin therapy. Only 42.2% and 19.8% of respondents reported meeting the aerobic and strengthening exercise recommendations, respectively. Women with one child or currently pregnant expecting their first child were 1.51 times more likely (95% CI, 1.02, 2.25) to meet the aerobic exercise recommendations than those with two or more children. The most common reported barriers to lifestyle intervention participation were “lack of time” (71.4%) and “childcare” commitments (57.7%). Lifestyle interventions delivered between 6 and 12 months postpartum (59.0%), involving an exercise program (82.6%), and delivered one-on-one were the most popular (64.9%). Conclusion: Most women report managing their GDM with lifestyle strategies. The most common strategies reported involve approaches not currently included in the clinical practice guidelines such as reducing carbohydrate consumption. Furthermore, despite being willing to participate in lifestyle interventions, respondents report significant barriers, including lack of time and childcare commitments, whereas mentioned supports included having an online format. Lifestyle interventions for women with a history of GDM should be designed in a manner that is both tailored to the individual and considerate of existing barriers and supports to participation.

Objectives: We investigated whether a Mediterranean-style diet (MedDiet) supplemented with fish oil can improve mental health in adults suffering depression. Methods: Adults with self-reported depression were randomized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months, or attend social groups fortnightly for 3 months. Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis. Results: n = 152 eligible adults aged 18–65 were recruited (n = 95 completed 3-month and n = 85 completed 6-month assessments). At 3 months, the MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P = 0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = −2.10, P = 0.04) and red meat/chicken (t = −2.13, P = 0.04). The MedDiet group had greater reduction in depression (t = −2.24, P = 0.03) and improved mental health QoL scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were sustained at 6 months. Reduced depression was correlated with an increased MedDiet score (r = −0.298, P = 0.01), nuts (r = −0.264, P = 0.01), and vegetable diversity (r = −0.303, P = 0.01). Other mental health improvements had similar correlations, most notably for increased vegetable diversity and legumes. There were some correlations between increased omega-3, decreased omega-6 and improved mental health. Discussion: This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression. Refereed/Peer-reviewed

An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode speciesC. briggsae(Cbr) andC. elegans(Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs withinCbrDCC recruitment sites that are highly enriched on X: 13-bp MEX and 30-bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated bindingin vivo. Hence, DCC binding toCbrrecruitment sites appears additive. In contrast, DCC binding toCelrecruitment sites is synergistic: mutating even one motifin vivoeliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstratedin vivoandin vitro. A single nucleotide position inCbrMEX can determine whetherCelDCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with conservation of target specificity for X-chromosome dosage compensation acrossDrosophilaspecies and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.

An accurate dietary fish questionnaire can be used to predict dietary intake status of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). The aim of this study was to design and validate a food frequency questionnaire (FFQ) to predict fish consumption of primary school children against a 7-day food diary (7d FD). A cross-sectional study was performed in elementary school in Surakarta, Indonesia. A total of 164 children aged 8 to 12 yo which were recruited using multi-stage random sampling were participated in this study. The FFQ consisted of 38 species of fish including 27 species of fresh fish and 11 species of processed fish. Total median (interquartile range) fish intake determined from the FFQ vs 7d FD was similar of 60 (36-114) g/d and 59 (37-108) g/d, respectively. A very good correlation was found between the FFQ and 7d FD by Spearman’s correlation coefficient test (r=0.965, p=0.0001) with an acceptable of the two methods using non-parametric limit of agreement (95% LoA=-10.907-34.619, median difference=0.011, 95% CI for median difference=-2.408-1.193). The FFQ is acceptable a valid tool to determine fish intake in this group.

BACKGROUD/OBJECTIVES Understanding the factors associated with fish consumption is necessary to determine strategies to improve the fish consumption particularly those high in omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). The aim of this study was to analyse the correlation between a mother's perspective on fish and actual fish consumption in their children. SUBJECTS/METHODS Two hundred thirty-one elementary school children grade 3-6 and their mothers in Surakarta were recruited using multi stage random sampling for this study. Data was collected in July and August 2017. A validated questionnaire consisted of 3 topics including knowledge related to the health benefits and organoleptic properties of fish and cooking technique-related attitudes on fish were used to measure the mother's response to the fish properties. A validated food frequency questionnaire and a food picture book of fish specifically designed for the survey were developed and used to assess fish consumption of the children. A χ2 test was used to analyse the correlation between the mothers' perspective on fish and their children's fish consumption. RESULTS The median fish consumption in children was 65 g/d with fried non-oily or lean fish, e.g., milkfish (locally called Bandeng) and catfish (locally called Lele) were consumed more than oily fish as well as processed fish products. Of all children, 31% met the fish consumption recommended by the Environmental Protection Agency-Food and Drug Administration 2017. There was no relationship between a mother's knowledge related to health benefits, organoleptic properties and cooking technique-related attitude toward fish and her child's fish consumption. CONCLUSIONS The fish consumption of children is not influenced by their mother's perspective on fish. Nutrition education strategies are warranted to improve fish consumption and maintain the optimal benefits by consuming fish, including fish high in n-3 LCPUFA.

Organisms that count X-chromosome number to determine sex utilize dosage compensation mechanisms to balance X-gene expression between sexes. Typically, a regulatory complex is recruited to X chromosomes of one sex to modulate gene expression. A major challenge is to determine the mechanisms that target regulatory complexes specifically to X. Here, we identify critical X-sequence motifs inCaenorhabditis elegansthat act synergistically in hermaphrodites to direct X-specific recruitment of the dosage compensation complex (DCC), a condensin complex. We find two DNA motifs that collaborate with a previously defined 12-bp motif called MEX (motif enriched on X) to mediate binding: MEX II, a 26-bp X-enriched motif and Motif C, a 9-bp motif that lacks X enrichment. Inserting both MEX and MEX II into a new location on X creates a DCC binding site equivalent to an endogenous recruitment site, but inserting only MEX or MEX II alone does not. Moreover, mutating MEX, MEX II, or Motif C in endogenous recruitment sites with multiple different motifs dramatically reduces DCC binding in vivo to nearly the same extent as mutating all motifs. Changing the orientation or spacing of motifs also reduces DCC binding. Hence, synergy in DCC binding via combinatorial clustering of motifs triggers DCC assembly specifically on X chromosomes. Using an in vitro DNA binding assay, we refine the features of motifs and flanking sequences that are critical for DCC binding. Our work reveals general principles by which regulatory complexes can be recruited across an entire chromosome to control its gene expression.

DNA topology and alternative DNA structures are implicated in regulating diverse biological processes. Although biomechanical properties of these structures have been studied extensively in vitro, characterization in vivo, particularly in multicellular organisms, is limited. We devised new methods to map DNA supercoiling and single-stranded DNA in Caenorhabditis elegans embryos and diapause larvae. To map supercoiling, we quantified the incorporation of biotinylated psoralen into DNA using high-throughput sequencing. To map single-stranded DNA, we combined permanganate treatment with genome-wide sequencing of induced double-stranded breaks. We found high levels of negative supercoiling at transcription start sites (TSSs) in embryos. GC-rich regions flanked by a sharp GC-to-AT transition delineate boundaries of supercoil propagation. In contrast to TSSs in embryos, TSSs in diapause larvae showed dramatic reductions in negative supercoiling without concomitant attenuation of transcription, suggesting developmental-stage-specific regulation. To assess whether alternative DNA structures control chromosome architecture and gene expression, we examined DNA supercoiling in the context of X-Chromosome dosage compensation. We showed that the condensin dosage compensation complex creates negative supercoils locally at its highest-occupancy binding sites but found no evidence for large-scale supercoiling domains along X Chromosomes. In contrast to transcription-coupled negative supercoiling, single-strandedness, which is most pronounced at transcript end sites, is dependent on high AT content and symmetrically positioned nucleosomes. We propose that sharp transitions in sequence composition at functional genomic elements constitute a common regulatory code and that DNA structure and propagation of torsional stress at regulatory elements are critical parameters in shaping important developmental events.

Maintaining blood glucose within the target range is the primary treatment goal for women with gestational diabetes mellitus (GDM). Foods with low glycaemic loads are recommended in clinical practice; however, the relative importance of other key lifestyle variables is unexplored. This pilot study explored the associations of glycaemic load, carbohydrates and physical activity parameters on blood glucose concentrations in free-living women with GDM. Twenty-nine women (28–30 weeks gestation, 34 ± 4 years) with GDM were enrolled. Continuous glucose monitoring, physical activity (ActivPAL inclinometer) and dietary intake and dietary quality were measured concurrently for 3 days. Pearson correlation analyses determined the association between glucose levels and lifestyle variables. Despite all receiving the same nutrition education, only 55% of women were following a low glycaemic load diet with a large range of carbohydrate intakes (97–267 g/day). However, the glycaemic load did not correlate with 3-hr postprandial glucose (r2 = 0.021, p = 0.56) or 24-h glucose iAUC (r2 = 0.021, p = 0.58). A significant relationship between total stepping time and lower 24-h glucose iAUC (r2 = 0.308, p = 0.02) and nocturnal glucose (r2 = 0.224, p = 0.05) was found. In free-living women with diet-controlled GDM, more physical activity, i.e., steps accumulated across the day, may be a simple and effective strategy for improving maternal blood glucose concentrations.

There is equivocal evidence about beneficial properties of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) for older adults. This study investigated the relationship between circulating ω-3 LCPUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels and their corresponding dietary intakes with cognition and physical function in a cohort of community-dwelling older adults at risk of dementia. A cross-sectional analysis was conducted among 142 community-dwelling older adults (60–85 years) with subjective memory complaints. Erythrocyte fatty acids (ω-3 LCPUFA) and the omega-3 index were measured; dietary DHA and EPA were assessed with a LCPUFA specific questionnaire. Cognition was measured using the Cogstate computerised battery and Trail-making tests. Muscle strength was assessed by grip strength and physical function via the four-square step test, 30-second sit-to-stand, timed up-and-go test, and 4-m walk test. Multiple regression analysis was used to assess the relationship between erythrocyte ω-3 LCPUFA, dietary intake, cognitive and physical function. Higher dietary DHA and EPA were associated with better global cognitive function (DHA: β=0.164, p=0.042; EPA: β=0.188, p=0.020). Higher dietary EPA was associated with better attention/psychomotor composite scores (β=0.196, p=0.024), mobility (four-square step test: β=−0.202, p=0.015) and gait speed (4m walk test: β=−0.200, p=0.017). No associations were found between erythrocyte ω-3 LCPUFA and cognitive or functional performance measures. In community-dwelling older adults with subjective memory complaints, higher dietary ω-3 LCPUFA intake was associated with better cognitive and physical function, supporting the evidence that ω-3 fatty acids play a role in optimising physical and cognitive health during ageing.

People classified as ultra-high risk (UHR) of developing psychosis have reduced cellular membrane omega-3 and omega-6 polyunsaturated fatty acids (PUFA). We aimed to compare omega-3 index, fatty acids and molecular phospholipid species from erythrocytes of people with UHR (n = 285) with age-matched healthy controls (n = 120) assessed by mass spectrometry. Lower proportions of PUFA were observed in the UHR group compared to healthy controls; specifically, eicosapentaenoic acid (EPA) was 29.3% lower, docosahexaenoic acid (DHA) was 27.2% lower, arachidonic acid (AA) was 15.8% lower and the omega-3 index was 26.9% lower. The AA to EPA ratio was higher in the UHR group compared to the healthy group. Smoking status had no significant effect on PUFA levels in healthy or the UHR groups. BMI was associated with PUFA levels in the UHR group only and the statistical model only explains 2% of the variance of the PUFA levels. The proportion of nervonic acid was 64.4% higher in the UHR group compared to healthy controls. At a lipid class level, the UHR group had 16% higher concentrations of sphingomyelin (SM) and 46% lower concentrations phosphatidylethanolamine (PE) compared to healthy group. Of the 49 individual molecular phospholipids, twenty-seven phospholipid species were lower in the UHR group. In conclusion, there are clear differences in the proportions of erythrocyte fatty acids and phospholipids between UHR and healthy controls and UHR had higher concentrations of SM and lower concentrations of PE. These differences may represent a promising prodromal risk biomarker in the UHR population to aid clinical diagnosis.

Omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) are necessary for optimum mental health, with recent studies showing low n-3 LCPUFA in people at ultra-high risk (UHR) of developing psychosis. Furthermore, people at UHR of psychosis had increased erythrocyte sphingomyelin (SM) and reduced phosphatidylethanolamine (PE) concentrations as well as 27 erythrocyte phospholipid species that differed when compared to erythrocytes from age matched people not at UHR of psychosis. The aim of this analysis was to evaluate the effect of n-3 supplementation on the different erythrocyte lipid species (including SM and PE concentrations) in people at UHR of psychosis. Participants were randomly assigned to fish oil (containing 840 mg EPA and 560 mg DHA per day) or placebo (paraffin oil) for 6 months. Fasted blood samples were taken at baseline and post intervention. Mass spectrometry was used to analyse the molecular phospholipids and fatty acid composition of erythrocytes for both groups. The n-3 index was significantly increased from 3.0% to 4.12% after 6 months of receiving n-3 capsules. Fish oil capsules increased the phospholipid molecular species containing n-3 LCPUFA, and concomitant decreases in n-6 LCPUFA species. SM species did not show any significant changes in n-3 LCPUFA group however, three SM species (SM 16:0, SM 18:0, SM 18:1) significantly increased after 6 months of supplementation with placebo. N-3 supplementation for 6 months led to higher n-3 incorporation into erythrocytes, at the expense of n-6 PUFA across all phospholipid classes analyzed and may have prevented the increase in SM seen in the placebo group.

Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) are critical for cell membrane structure and function. Human beings have a limited ability to synthesise docosahexaenoic acid (DHA), the main n-3 LCPUFA required for neurological development. Inadequate levels of n-3 LCPUFA can affect the dopaminergic system in the brain and, when combined with genetic and other factors, increase the risk of developing aggression, inattention and impulse-control disorders. In this study, male prisoners were administered questionnaires assessing aggressive behaviour and executive functions. Participants also produced blood sampling for the measurement of the Omega-3 Index and the genotyping of dopaminergic genetic variants. Significant associations were found between functional genetic polymorphism in DBH rs1611115 and verbal aggression and between DRD2 rs4274224 and executive functions. However, the Omega-3 Index was not significantly associated with the tested dopaminergic polymorphisms. Although previous interactions between specific genotypes and n-3 LCPUFA were previously reported, they remain limited and poorly understood. We did not find any association between n-3 LCPUFA and dopaminergic polymorphisms in adult male prisoners; however, we confirmed the importance of genetic predisposition for dopaminergic genes (DBH and DRD2) in aggressive behaviour, memory dysfunction and attention-deficit disorder.

Supplementation of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) may enhance self-regulation (SR) and executive functioning (EF) in children of preschool age. The aim of the Omega Kid Study was to investigate the effect of n-3 LCPUFA supplementation on SR and EF in typically developing preschool-aged children. A double-blind placebo-controlled pilot trial was undertaken, the intervention was 12 weeks and consisted of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day compared to placebo. The HS-Omega-3 Index® was assessed by capillary blood samples at baseline and post-intervention. Seventy-eight children were enrolled and randomised to either the n-3 LCPUFA treatment (n = 39) or placebo (n = 39) group. Post intervention, there was a significant three-fold increase in the HS-Omega-3 Index® in the n-3 LCPUFA group (p &lt, 0.001). There were no improvements in SR or EF outcome variables for the n-3 LCPUFA group post intervention compared to the placebo group determined by linear mixed models. At baseline, there were significant modest positive Spearman correlations found between the HS-Omega-3 index® and both behavioural self-regulation and cognitive self-regulation (r = 0.287, p = 0.015 and r = 0.242, p = 0.015 respectively). Although no treatment effects were found in typically developing children, further research is required to target children with sub-optimal self-regulation who may benefit most from n-3 LCPUFA supplementation.

Nuclei are central hubs for information processing in eukaryotic cells. The need to fit large genomes into small nuclei imposes severe restrictions on genome organization and the mechanisms that drive genome-wide regulatory processes. How a disordered polymer such as chromatin, which has vast heterogeneity in its DNA and histone modification profiles, folds into discernibly consistent patterns is a fundamental question in biology. Outstanding questions include how genomes are spatially and temporally organized to regulate cellular processes with high precision and whether genome organization is causally linked to transcription regulation. The advent of next-generation sequencing, super-resolution imaging, multiplexed fluorescent in situ hybridization, and single-molecule imaging in individual living cells has caused a resurgence in efforts to understand the spatiotemporal organization of the genome. In this review, we discuss structural and mechanistic properties of genome organization at different length scales and examine changes in higher-order chromatin organization during important developmental transitions. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Context Maternal body mass index (BMI) is associated with increased birth weight but does not explain all the variance in fetal adiposity. Objective To assess the contribution of maternal body fat distribution to offspring birth weight and adiposity. Design Longitudinal study throughout gestation and at delivery. Setting Women recruited at 12 weeks of gestation and followed up at 26 and 36 weeks. Cord blood was collected at delivery. Patients Pregnant women (n = 45) with BMI 18.0 to 46.3 kg/m2 and healthy pregnancy outcome. Methods Maternal first trimester abdominal subcutaneous and visceral adipose tissue thickness (SAT and VAT) was assessed by ultrasound. Main Outcome Measures Maternal body fat distribution, maternal and cord plasma glucose and lipid concentrations, placental weight, birth weight, and fetal adiposity assessed by cord blood leptin. Results VAT was the only anthropometric measure independently associated with birth weight centile (r2 adjusted 15.8%, P = .002). BMI was associated with trimester 2 and trimesters 1 through 3 area under the curve (AUC) glucose and insulin resistance (Homeostatic Model Assessment). SAT alone predicted trimester 2 lipoprotein lipase (LPL) mass (a marker of adipocyte insulin sensitivity) (11.3%, P = .017). VAT was associated with fetal triglyceride (9.3%, P = .047). Placental weight was the only independent predictor of fetal adiposity (48%, P < .001). Maternal trimester 2 and AUC LPL were inversely associated with fetal adiposity (r = -0.69, P = .001 and r = -0.58, P = .006, respectively). Conclusions Maternal VAT provides additional information to BMI for prediction of birth weight. VAT may be a marker of reduced SAT expansion and increased availability of maternal fatty acids for placental transport.

Numerous health benefits are attributed to the n-3 long-chain PUFA (n-3 LCPUFA); EPA and DHA. A systematic literature review was conducted to investigate factors, other than diet, that are associated with the n-3 LCPUFA levels. The inclusion criteria were papers written in English, carried out in adult non-pregnant humans, n-3 LCPUFA measured in blood or tissue, data from cross-sectional studies, or baseline data from intervention studies. The search revealed 5076 unique articles of which seventy were included in the qualitative synthesis. Three main groups of factors potentially associated with n-3 LCPUFA levels were identified: (1) unmodifiable factors (sex, genetics, age), (2) modifiable factors (body size, physical activity, alcohol, smoking) and (3) bioavailability factors (chemically bound form of supplements, krill oil v. fish oil, and conversion of plant-derived α-linolenic acid (ALA) to n-3 LCPUFA). Results showed that factors positively associated with n-3 LCPUFA levels were age, female sex (women younger than 50 years), wine consumption and the TAG form. Factors negatively associated with n-3 LCPUFA levels were genetics, BMI (if erythrocyte EPA and DHA levels are v. fish oil associated with n-3 LCPUFA levels is inconclusive. There is also evidence that higher ALA consumption leads to increased levels of EPA but not DHA. In conclusion, sex, age, BMI, alcohol consumption, smoking and the form of n-3 LCPUFA are all factors that need to be taken into account in n-3 LCPUFA research.

Irritability and hyperactivity are common in children with Autism Spectrum Disorder (ASD). Because pharmacological treatments may have adverse effects, and despite limited evidence, caregivers/parents often use dietary supplements such as vitamin D and omega-3 fatty acids to address these behavioural symptoms. As a secondary objective of the VIDOMA (Vitamin D and Omega-3 in ASD) trial, we evaluated the efficacy of vitamin D, omega-3 long chain polyunsaturated fatty acid [omega-3 LCPUFA; docosahexaenoic acid (DHA)], or both on irritability and hyperactivity. New Zealand children with ASD (aged 2.5-8 years) participated in a 12-month randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day, VID), omega-3 LCPUFA (722 mg/day DHA, OM), or both (2000 IU/day vitamin D + 722 mg/day DHA, VIDOM). The primary outcomes were the Aberrant Behaviour Checklist (ABC) domains of irritability and hyperactivity. Biomarkers (serum 25-hydroxyvitamin D [25(OH)D] and omega-3 index) and primary outcomes were measured at baseline and 12-months. Out of 111 children who completed baseline data collection, 66% completed the study (VID = 19, OM = 23, VIDOM = 15, placebo = 16). After 12 months, children receiving OM (-5.0 ± 5.0, P = 0.001) and VID (-4.0±4.9, P = 0.01) had greater reduction in irritability than placebo (0.8±6.1). Compared to placebo, children on VID also had greater reduction in hyperactivity (-5.2±6.3 vs. -0.8±5.6, P = 0.047). Serum 25(OH)D concentration (nmol/L, mean±SD) increased by 27±14 in VID and by 36±17 in VIDOM groups (P 0.0001), and omega-3 index (%, median (25th, 75th percentiles)) by 4.4 (3.3, 5.9) in OM and by 4.0 (2.0, 6.0) in VIDOM groups (P 0.0001), indicating a good compliance rate. The results indicate that vitamin D and omega-3 LCPUFA reduced irritability symptoms in children with ASD. Vitamin D also reduced hyperactivity symptoms in these children.

We evaluated the efficacy of vitamin D (VID), omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA, OM), or both (VIDOM) on core symptoms of ASD. New Zealand children with ASD (n = 73; aged 2.5–8.0 years) received daily 2000 IU vitamin D3, 722 mg docosahexaenoic acid, both, or placebo. Outcome measures were Social Responsiveness Scale (SRS) and Sensory Processing Measure (SPM). Of 42 outcome measures comparisons (interventions vs. placebo), two showed greater improvements (P = 0.03, OM and VIDOM for SRS-social awareness) and four showed trends for greater improvements (P

Seaweed polysaccharides in the diet may influence both inflammation and the gut microbiome. Here we describe two clinical studies with an Ulva sp. 84-derived sulfated polysaccharide—“xylorhamnoglucuronan” (SXRG84)—on metabolic markers, inflammation, and gut flora composition. The first study was a double-blind, randomized placebo-controlled trial with placebo, and either 2 g/day or 4 g/day of SXRG84 daily for six weeks in 64 overweight or obese participants (median age 55 years, median body mass index (BMI) 29 kg/m2). The second study was a randomized double-blind placebo-controlled crossover trial with 64 participants (median BMI 29 kg/m2, average age 52) on placebo for six weeks and then 2 g/day of SXRG84 treatment for six weeks, or vice versa. In Study 1, the 2 g/day dose exhibited a significant reduction in non-HDL (high-density lipoprotein) cholesterol (−10% or −0.37 mmol/L, p = 0.02) and in the atherogenic index (−50%, p = 0.05), and two-hour insulin (−12% or −4.83 mU/L) showed trends for reduction in overweight participants. CRP (C-reactive protein) was significantly reduced (−27% or −0.78 mg/L, p = 0.03) with the 4 g/day dose in overweight participants. Significant gut flora shifts included increases in Bifidobacteria, Akkermansia, Pseudobutyrivibrio, and Clostridium and a decrease in Bilophila. In Study 2, no significant differences in lipid measures were observed, but inflammatory cytokines were improved. At twelve weeks after the SXRG84 treatment, plasma cytokine concentrations were significantly lower than at six weeks post placebo for IFN-γ (3.4 vs. 7.3 pg/mL), IL-1β (16.2 vs. 23.2 pg/mL), TNF-α (9.3 vs. 12.6 pg/mL), and IL-10 (1.6 vs. 2.1 pg/mL) (p < 0.05). Gut microbiota abundance and composition did not significantly differ between groups (p > 0.05). Together, the studies illustrate improvements in plasma lipids and an anti-inflammatory effect of dietary SXRG84 that is participant specific.

“Life 2.0” may sound like hyperbole—suggesting a radical change in modes of existence—but that was the title of a Colloquium held at the Beckman Center in Irvine, California, in December 2019. The subtitle, “The Promise and Challenge of a CRISPR Path to a Sustainable Planet,” was both more modest and a more apt description of the proceedings. Sponsored by the National Academy of Sciences and organized by us with Fyodor Urnov, the event drew speakers from numerous disciplines who offered visions of the near and more distant future of life on Earth. Several papers based on Colloquium presentations are included in this issue of PNAS. In the keynote address, “A view from the edge,” D.C. reviewed the context and history of genome editing and set the stage for projecting into the future. In the first session, titled “The translational promise of CRISPR and the urgency of the challenge,” Michele Calos highlighted the need for precise, affordable human therapies that go beyond “classical” gene therapy. Jonathan Weissman described a powerful, CRISPR-based approach to tracking metastatic lung cancer cells. B.J.M. showed how studies in model organisms can provide insights into human biology and disease, sometimes through surprising connections. Peter Hotez prophetically envisioned the arrival of a new epidemic, including the political, social, and physical challenges in delivering vaccines. Pamela C. Ronald addressed the particularly urgent need for genetic modifications in crops to help ameliorate the impact of climate change and the threats to world food supplies, as described in … [↵][1]1To whom correspondence may be addressed. Email: dana{at}biochem.utah.edu. [1]: #xref-corresp-1-1

We demonstrate how RNA binding protein FOX-1 functions as a dose-dependent X-signal element to communicate X-chromosome number and thereby determine nematode sex. FOX-1, an RNA recognition motif protein, triggers hermaphrodite development in XX embryos by causing non-productive alternative pre-mRNA splicing ofxol-1, the master sex-determination switch gene that triggers male development in XO embryos. RNA binding experiments together with genome editing demonstrate that FOX-1 binds to multiple GCAUG and GCACG motifs in axol-1intron, causing intron retention or partial exon deletion, thereby eliminating male-determining XOL-1 protein. Transforming all motifs to GCAUG or GCACG permits accurate alternative splicing, demonstrating efficacy of both motifs. Mutating subsets of both motifs partially alleviates non-productive splicing. Mutating all motifs blocks it, as does transforming them to low-affinity GCUUG motifs. Combining multiple high-affinity binding sites with the twofold change in FOX-1 concentration between XX and XO embryos achieves dose-sensitivity in splicing regulation to determine sex.

Background Interventions to better manage aggressive behaviour and reduce recidivism are a primary concern for corrective services. Nutritional interventions to correct prisoner behaviour have been largely overlooked in the literature. Emerging evidence suggests that dietary intake influences aggressive behaviours and that nutritional supplementation with omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) could attenuate both the severity and frequency of aggressive behaviour. Methods Adult male prisoners who have a history of aggressive behaviour (n = 600) will be recruited from at least 6 Correctional Centres and randomised to receive either n-3 LCPUFA or placebo supplementation for a 16-week duration. Treatment will be with either 1 g/day of n-3 LCPUFA (694 mg DHA and 397 mg EPA) or placebo capsules, which are a corn/soy oil blend and are identical in size and colour. The primary outcome measure is the Inmate Behavioural Observation Scale (IBOS): an objective measure of aggressive behaviour. Secondary outcome measures include questionnaires (including aggression, attention deficit disorder, impulsivity, depression/anxiety/stress scales), engagement in programmes, recidivism and quality of life. Baseline and post-intervention assessments include the IBOS, questionnaires and blood to measure the levels of n-3 LCPUFA. Discussion To conclusively test the potential that increasing n-3 LCPUFA intakes can improve rates of prisoner aggression and associated mental health and violence-related social system management costs, we propose an adequately powered multi-centre, double-blind, randomised controlled trial, examining the effects of n-3 LCPUFA supplementation on aggressive behaviour in adult male prisoners. If successful, this study will inform prisoner policy with respect to nutrition and by inference contribute to a broader community approach to preventative mental health practices. Trial registration Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN12618001665224. Registered on 10 October 2018.

Omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation in the cardiovascular field is effective if a certain Omega-3 index (O3I) is achieved or the daily n-3 LCPUFA dose is high enough. Whether this applies to studies on cognition in children and adolescents is unclear. The aims of the current review were to investigate whether: (1) a certain O3I level and (2) a minimum daily n-3 LCPUFA dose are required to improve cognition in 4–25 year olds. Web of Science and PubMed were searched. Inclusion criteria: placebo controlled randomized controlled trial; participants 4–25 years; supplementation with docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA); assessing cognition; in English and ≥10 participants per treatment arm. Thirty-three studies were included, 21 in typically developing participants, 12 in those with a disorder. A positive effect on cognitive measures was more likely in studies with an increase in O3I to >6%. Half of the studies in typically developing children with daily supplementation dose ≥450 mg DHA + EPA showed improved cognition. For children with a disorder no cut-off value was found. In conclusion, daily supplementation of ≥450 mg DHA + EPA per day and an increase in the O3I to >6% makes it more likely to show efficacy on cognition in children and adolescents.

We demonstrate how RNA binding protein FOX-1 functions as a dose-dependent X-signal element to communicate X-chromosome number and thereby determine nematode sex. FOX-1, an RNA recognition motif protein, triggers hermaphrodite development in XX embryos by causing non-productive alternative pre-mRNA splicing of xol-1, the master sex-determination switch gene that triggers male development in XO embryos. RNA binding experiments together with genome editing demonstrate that FOX-1 binds to multiple GCAUG and GCACG motifs in a xol-1 intron, causing intron retention or partial exon deletion, thereby eliminating male-determining XOL-1 protein. Transforming all motifs to GCAUG or GCACG permits accurate alternative splicing, demonstrating efficacy of both motifs. Mutating subsets of both motifs partially alleviates non-productive splicing. Mutating all motifs blocks it, as does transforming them to low-affinity GCUUG motifs. Combining multiple high-affinity binding sites with the twofold change in FOX-1 concentration between XX and XO embryos achieves dose-sensitivity in splicing regulation to determine sex.

Background: Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis. Methods: A total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. Results: The n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms. Conclusions: Partially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group. Clinical Trial Registration: ANZCTR, identifier: 12608000475347.

Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important for neurological development. The aim was to determine the distribution and relative enrichment of AA and DHA among lipoprotein fractions prior to pregnancy, throughout gestation and in the post-partum period. Our hypothesis was that in pregnancy, in contrast to the non-pregnant state, AA and DHA are carried in highest concentration in the very low density lipoprotein (VLDL) fraction secondary to increased gestational liver triglyceride secretion. Two independent prospective, observational cohort studies carried out in Glasgow were combined; one early in pregnancy and one later in pregnancy with post-partum follow up. Across the pregnancy timeline plasma lipoproteins were isolated using sequential ultracentrifugation and lipoprotein fatty acids were extracted and analysed by gas chromatography. High density lipoprotein (HDL) had the highest concentration of AA and DHA compared to other lipoproteins. HDL became progressively enriched in the proportion of triglycerides at 16 weeks of gestation, which peaked at 35 weeks and returned to baseline at 13 weeks postpartum. HDL DHA per HDL-cholesterol and HDL DHA per apoA-I became progressively enriched at 16 weeks of gestation, peaked at 25 weeks and returned to baseline at 13 weeks postpartum, whereas HDL AA (per HDL-C or HDL-apoA-I) did not differ. DHA is carried primarily in HDL rather than VLDL. HDL has anti-oxidant properties that might afford DHA protection against oxidation.

Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization in Caenorhabditis elegans and investigate roles for compartments in regulating gene expression. Distal arms of C. elegans chromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other both in cis and in trans, while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genes met-2 and set-25 significantly impaired formation of inactive Arm and active Center compartments. cec-4 mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote their cis association, and an anchoring-independent mechanism that compacts individual chromosome arms. In both met-2 set-25 and cec-4 mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.

The prostate is surrounded by periprostatic adipose tissue (PPAT), the thickness of which has been associated with more aggressive prostate cancer (PCa). There are limited data regarding the functional characteristics of PPAT, how it compares to subcutaneous adipose tissue (SAT), and whether in a setting of localized PCa, these traits are altered by obesity or disease aggressiveness. PPAT and SAT were collected from 60 men (age: 42&ndash, 78 years, BMI: 21.3&ndash, 35.6 kg/m2) undergoing total prostatectomy for PCa. Compared to SAT, adipocytes in PPAT were smaller, had the same basal rates of fatty acid release (lipolysis) yet released less polyunsaturated fatty acid species, and were more sensitive to isoproterenol-stimulated lipolysis. Basal lipolysis of PPAT was increased in men diagnosed with less aggressive PCa (Gleason score (GS) &le, 3 + 4) compared to men with more aggressive PCa (GS &ge, 4 + 3) but no other measured adipocyte parameters related to PCa aggressiveness. Likewise, there was no difference in PPAT lipid biology between lean and obese men. In conclusion, lipid biological features of PPAT do differ from SAT, however, we did not observe any meaningful difference in ex vivo PPAT biology that is associated with PCa aggressiveness or obesity. As such, our findings do not support a relationship between altered PCa behavior in obese men and the metabolic reprogramming of PPAT.

Background: The role of vitamin D and omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA) in improving core symptoms of autism spectrum disorder (ASD) in children has been investigated by a few randomised controlled trials and the results are mixed and inconclusive. The response to treatment with these nutrients is heterogenous and may be influenced by inflammatory state. As an exploratory analysis, we investigated whether inflammatory state would modulate the effect of these nutrients on core symptoms of ASD. Methods: Seventy-three New Zealand children with ASD (2.5&ndash, 8.0 years) completed a 12-month randomised, double-blind, placebo-controlled trial of vitamin D (VID, 2000 IU/day), omega-3 LCPUFA, (OM, 722 mg/day docosahexaenoic acid), or both (VIDOM). Non-fasting baseline plasma interleukin-1&beta, (IL-1&beta, ) was available for 67 children (VID = 15, OM = 21, VIDOM = 15, placebo = 16). Children were categorised as having undetectable/normal IL-1&beta, (&lt, 3.2 pg/ml, n=15) or elevated IL-1&beta, (&ge, 3.2 pg/mL, n = 52). The Social Responsiveness Scale (SRS) questionnaire was used to assess core symptoms of ASD (baseline, 12-month). Mixed model repeated measure analyses (including all children or only children with elevated IL-1&beta, ) were used. Results: We found evidence for an interaction between baseline IL-1&beta, and treatment response for SRS-total, SRS-social communicative functioning, SRS-awareness and SRS-communication (all Pinteraction &lt, 0.10). When all children were included in the analysis, two outcome comparisons (treatments vs. placebo) showed greater improvements: VID, no effect (all P &gt, 0.10), OM and VIDOM (P = 0.01) for SRS-awareness. When only children with elevated IL-1&beta, were included, five outcomes showed greater improvements: OM (P = 0.01) for SRS-total, OM (P = 0.03) for SRS-social communicative functioning, VID (P = 0.01), OM (P = 0.003) and VIDOM (P = 0.01) for SRS-awareness. Conclusion: Inflammatory state may have modulated responses to vitamin D and omega-3 LCPUFA intervention in children with ASD, suggesting children with elevated inflammation may benefit more from daily vitamin D and omega-3 LCPUFA supplementation.

This study aimed to assess the feasibility of conducting a nutrition trial in adult male prisoners. Adult male prisoners were recruited for a 16-week randomised control trial comparing the effect of ingestion of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) and multivitamin supplements versus placebo on aggressive behaviour. The baseline and post-intervention assessments from the participant blood samples were the erythrocyte n-3 LCPUFA levels as well as measures of aggressive behaviour determined through institutional records of misconduct (IRM), the Inmate Behaviour Observation Scale (IBOS), and questionnaires. A total of 136 adult male prisoners consented to the study with a retention rate of 60%, and 93% of blood samples were successfully collected. The IRM and IBOS scores were collected for 100% of participants, whilst 82&ndash, 97% of participants completed the questionnaires. From the baseline data, the Odds Ratio shows that prisoners are 4.3 times more likely to have an IBOS &gt, 2 if they are below the 6% cut off on the omega-3 index. Both groups improved across all outcome measures and, at the current sample size, no significant differences were seen between them. A power calculation suggests a total sample size of 600 participants is required to detect the effects of this dietary supplementation, and that this supplementation study is feasible in a Correctional Centre. Important criteria for the exclusion and consideration of logistics and compliance are presented.

In consideration that, fatty acids bound within phospholipids may exhibit greater levels of bioavailability than neutral lipids, we investigated the effect of nutrient starvation on the phospholipid content and composition of cultivated Ulva biomass. Furthermore, we explored the simultaneous effects on the pigment and phenolic profiles and then correlation analysis to anti-oxidant and anti-inflammatory activity. High nutrient cultivation (nitrogen replete) provided a biomass with desirable n-6/n-3 (0.3) and 18:2n-6/18:3n-3 (0.5) ratios and beneficial 18:4n-3, 20:5n-3, 22:5n-3 fatty acids. These fatty acids dominated the abundant neutral lipid fraction, which comprised 62% of the lipid extract. The remaining phospholipids (38%) were characterised by high 16:0 (49.6%), 18:1n-7 (14.6%) and 18:3n-3 (13.6%) fatty acids. Nutrient-depleted samples had a 3-fold higher total fatty acid (TFA) content (12.05 mg·g−1 d.w, p

Aim To validate the polyunsaturated food frequency questionnaire (PUFA FFQ) and test for reproducibility in people with end stage renal disease on dialysis treatment. Methods Participants (n = 32) completed the PUFA FFQ and three 24-hour recalls. Erythrocyte samples (n = 29) were used for erythrocyte fatty acid analysis. The triangular relationship between the PUFA FFQ, 24-hour recalls and the biomarker was assessed using the method of triads. Agreement between the two dietary methods was also assessed using Bland-Altman plots and classification by quintiles. Reproducibility was tested on a subset of the group (n = 8). Results The PUFA FFQ was a valid measure of all PUFA except for docosapentaenoic acid (DPA) and arachidonic acid (AA). Strong validity coefficients were found for n-3 long-chain PUFA (LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of 0.914 (95% CI: 0.665, 0.997) and 0.889 (95% CI: 0.706, 0.994), respectively. In the Bland-Altman plots 91-100% of observations fell between the limits of agreement for all PUFA. There were significant correlations between the initial FFQ and the repeat FFQ for all PUFA except DPA and AA. Conclusions The PUFA FFQ is a valid tool for assessing PUFA intake in people with end stage renal disease.

The environment for embryo implantation and fetal growth and development is affected by maternal nutritional, metabolic and health status. The aim of this prospective, cohort study was to test whether plasma metabolic and inflammatory biomarkers can predict pregnancy resulting from in vitro fertilisation (IVF). Women with a natural menstrual cycle undergoing frozen embryo transfer (FET) were recruited and fasting baseline blood samples were collected a mean of 3.4 days prior to the luteinising hormone (LH) surge and a non-fasting blood sample was taken on the day of FET. Ongoing pregnancy was defined by positive fetal heartbeat on ultrasound scan at day 45 post LH surge. Thirty-six pregnancies resulted from FET in 143 women. In an overall stepwise multivariable analysis, erythrocyte saturated to unsaturated fatty acid ratio was positively associated with ongoing pregnancy. A similar model incorporating day of FET covariates found that erythrocyte saturated to unsaturated fatty acid ratio, erythrocyte fatty acid average chain length and plasma log-triglycerides predicted ongoing pregnancy. In conclusion, a higher peri-conceptional saturated to unsaturated fatty acid ratio predicted ongoing pregnancy after natural cycle frozen embryo transfer and may reflect a maternal nutritional status that facilitates pregnancy success in this assisted conception scenario.

Determining sex is a binary developmental decision that most metazoans must make. Like many organisms, Caenorhabditis elegans specifies sex (XO male or XX hermaphrodite) by tallying X-chromosome number. We dissected this precise counting mechanism to determine how tiny differences in concentrations of signals are translated into dramatically different developmental fates. Determining sex by counting chromosomes solved one problem but created another—an imbalance in X gene products. We found that nematodes compensate for the difference in X-chromosome dose between sexes by reducing transcription from both hermaphrodite X chromosomes. In a surprising feat of evolution, X-chromosome regulation is functionally related to a structural problem of all mitotic and meiotic chromosomes: achieving ordered compaction of chromosomes before segregation. We showed the dosage compensation complex is a condensin complex that imposes a specific three-­dimensional architecture onto hermaphrodite X chromosomes. It also triggers enrichment of histone modification H4K20me1. We discovered the machinery and mechanism underlying H4K20me1 enrichment and demonstrated its pivotal role in regulating higher-order X-chromosome structure and gene expression.