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Pomegranate (Punica granatum L., Punicaceae) fruit is traditionally consumed in several countries, especially in Middle East, and has gained increasing popularity all over the world due to its assumed health benefits. Juices derived from the arils of the seeds were shown to be rich in anthocyanin glucosides, typically composed of cyanidin, delphinidin, and pelargonidin. The aim of the present study was the characterization of diverse Sicilian and Spanish pomegranate accessions regarding their anthocyanin and total polyphenol contents using the Folin-Ciocalteu reagent. The anthocyanin profiles were determined by HPLC-DAD and LC-MS, and color parameters were characterized using the CIELAB coordinates. Antioxidant activities were measured using a fluorimetric assay, and expressed as ORAC values. The anthocyanin and polyphenol contents were correlated with their antioxidant activities. Results obtained were correlated and evaluated for the identification of the most suitable accessions to be selected for cultivation, juice processing, and further breeding. [ABSTRACT FROM AUTHOR]

Background -- Numerous epidemiological studies have revealed a positive correlation between a diet rich in fruits and vegetables and a decreased incidence of certain degenerative diseases. Therefore, research interest has been focused on plant secondary metabolites, such as polyphenolics and carotenoids, which have been shown to exert certain health-beneficial effects. There is a need to find commercially appropriate means to isolate and concentrate these compounds as ingredients for functional or enriched foods. Objective -- The objective of this study was to systematically investigate the effect of various parameters on the adsorption and desorption behaviour of monomeric and polymeric phenolic compounds using a food grade polymeric adsorption resin. Design -- Batch adsorption experiments on a laboratory scale were conducted with fixed amounts of a diluted apple juice concentrate and weighed portions of a methacrylic resin under continuous stirring in a nitrogen atmosphere. The juice was allowed to be in contact with the resin until saturation conditions were achieved. Accelerated Solvent Extraction (ASE) technology was applied to study the elution efficiency of different solvents using resin which had been saturated with apple polyphenolics. Outcomes -- Although commonly applied in industrial processes there is still a lack of experimental data to predict performance thus making these processes empirical in nature. In contrast to previous findings on the adsorption behaviour of isolated flavonoids a lower pH value improved the adsorption efficiency. Moreover, a decrease in temperature and a higher feed concentration and juice : resin ratio increased the amount of phenolics bound to the resin. For the recovery of the compounds, the temperature during the elution step was the most important parameter besides the solvent composition. Conclusions -- The present study allows the development of efficient and cost-effective industrial processes that can also be applied to other matrices in order to fractionate and concentrate phenolic compounds for the production of tailor-made plant extract ingredients. [ABSTRACT FROM AUTHOR]

Artificial intelligence-guided closed-loop experimentation has emerged as a promising method for optimization of objective functions 1,2 , but the substantial potential of this traditionally black-box approach to uncovering new chemical knowledge has remained largely untapped. Here we report the integration of closed-loop experiments with physics-based feature selection and supervised learning, denoted as closed-loop transfer (CLT), to yield chemical insights in parallel with optimization of objective functions. CLT was used to examine the factors dictating the photostability in solution of light-harvesting donor-acceptor molecules used in a variety of organic electronics applications, and showed fundamental insights including the importance of high-energy regions of the triplet state manifold. This was possible following automated modular synthesis and experimental characterization of only around 1.5% of the theoretical chemical space. This physics-informed model for photostability was strengthened using multiple experimental test sets and validated by tuning the triplet excited-state energy of the solvent to break out of the observed plateau in the closed-loop photostability optimization process. Further applications of CLT to additional materials systems support the generalizability of this strategy for augmenting closed-loop strategies. Broadly, these findings show that combining interpretable supervised learning models and physics-based features with closed-loop discovery processes can rapidly provide fundamental chemical insights., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Wound healing is an obvious clinical concern that can be hindered by inadequate angiogenesis, inflammation, and chronic hypoxia. While exosomes derived from adipose tissue-derived stem cells have shown promise in accelerating healing by carrying therapeutic growth factors and microRNAs, intracellular cargo delivery is compromised in hypoxic tissues due to activated hypoxia-induced endocytic recycling. To address this challenge, we have developed a strategy to coat oxygen nanobubbles with exosomes and incorporate them into a polyvinyl alcohol/gelatin hybrid hydrogel. This approach not only alleviates wound hypoxia but also offers an efficient means of delivering exosome-coated nanoparticles in hypoxic conditions. The self-healing properties of the hydrogel, along with its component, gelatin, aids in hemostasis, while its crosslinking bonds facilitate hydrogen peroxide decomposition, to ameliorate wound inflammation. Here, we show the potential of this multifunctional hydrogel for enhanced healing, promoting angiogenesis, facilitating exosome delivery, mitigating hypoxia, and inhibiting inflammation in a male rat full-thickness wound model., (© 2024. The Author(s).)

Molecular hydrogen (H2) and formate (HCOO-) are metabolic end products of many primary fermenters in the rumen ecosystem. Both play a vital role in fermentation where they are electron sinks for individual microbes in an anaerobic environment that lacks external electron acceptors. If H2 and/or formate accumulate within the rumen, the ability of primary fermenters to regenerate electron carriers may be inhibited and microbial metabolism and growth disrupted. Consequently, H2- and/or formate-consuming microbes such as methanogens and possibly homoacetogens play a key role in maintaining the metabolic efficiency of primary fermenters. There is increasing interest in identifying approaches to manipulate the rumen ecosystem for the benefit of the host and the environment. As H2 and formate are important mediators of interspecies interactions, an understanding of their production and utilization could be a significant starting point for the development of successful interventions aimed at redirecting electron flow and reducing methane emissions. We conclude by discussing in brief ruminant methane mitigation approaches as a model to help understand the fate of H2 and formate in the rumen ecosystem.

Some animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent aberrant growth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Abidi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Diabetes, end stage renal disease (ESRD), and peripheral arterial disease (PAD) are associated with a higher risk of diabetes-related lower limb amputation. Timely identification of PAD with toe systolic blood pressure (TSBP) and toe-brachial pressure index (TBPI) is critical in order to implement foot protection strategies to prevent foot complications in people with ESRD. There is limited evidence describing the effect of haemodialysis on TSBP and TBPI. This study aimed to determine the variability of TSBP and TBPI during haemodialysis in people with ESRD, and to determine whether any observed variability differed between people with and without diabetes., Methods: TSBP and TBPI were taken before dialysis (T1), one hour into dialysis (T2) and in the last 15 min of dialysis (T3) during a single dialysis session. Linear mixed effects models were undertaken to determine the variability in TSBP and TBPI across the three time points and to determine whether this variability differed between people with and without diabetes., Results: Thirty participants were recruited, including 17 (57%) with diabetes and 13 (43%) with no diabetes. A significant overall reduction in TSBP was observed across all participants (P < 0.001). There was a significant reduction in TSBP between T1 and T2 (P < 0.001) and between T1 and T3 (P < 0.001). There was no significant overall change in TBPI over time (P = 0.62). There was no significant overall difference in TSBP between people with diabetes and people with no diabetes (mean difference [95% CI]: -9.28 [-40.20, 21.64], P = 0.54). There was no significant overall difference in TBPI between people with diabetes and people with no diabetes (mean difference [95% CI]: -0.01 [-0.17, 03.16], P = 0.91)., Conclusion: TSBP and TBPI are an essential part of vascular assessment of the lower limb. TBPI remained stable and TSBP significantly reduced during dialysis. Given the frequency and duration of dialysis, clinicians taking toe pressures to screen for PAD should be aware of this reduction and consider how this may have an impact on wound healing capacity and the development of foot related complications., (© 2023. The Author(s).)

Antibodies targeting specific bacterial species could allow for modification of the rumen microbial population to enhance rumen fermentation. However, there is limited knowledge of targeted antibody effects on rumen bacteria. Therefore, our objective was to develop efficacious polyclonal antibodies to inhibit the growth of targeted cellulolytic bacteria from the rumen. Egg-derived, polyclonal antibodies were developed against pure cultures of Ruminococcus albus 7 ( anti-RA7 ), Ruminococcus albus 8 ( anti-RA8 ), and Fibrobacter succinogenes S85 ( anti-FS85 ). Antibodies were added to a cellobiose-containing growth medium for each of the three targeted species. Antibody efficacy was determined via inoculation time (0 h and 4 h) and dose response. Antibody doses included: 0 ( CON ), 1.3 × 10 -4 ( LO ), 0.013 ( MD ), and 1.3 ( HI ) mg antibody per ml of medium. Each targeted species inoculated at 0 h with HI of their respective antibody had decreased ( P < 0.01) final optical density and total acetate concentration after a 52 h growth period when compared with CON or LO. Live/dead stains of R. albus 7 and F. succinogenes S85 dosed at 0 h with HI of their respective antibody indicated a decrease (≥ 96%; P < 0.05) in live bacterial cells during the mid-log phase compared with CON or LO. Addition of HI of anti-FS85 at 0 h in F. succinogenes S85 cultures reduced ( P < 0.01) total substrate disappearance over 52 h by at least 48% when compared with CON or LO. Cross-reactivity was assessed by adding HI at 0 h to non-targeted bacterial species. Addition of anti-RA8 or anti-RA7 to F. succinogenes S85 cultures did not affect ( P ≥ 0.45) total acetate accumulation after 52 h incubation, indicating that antibodies have less of an inhibitory effect on non-target strains. Addition of anti-FS85 to non-cellulolytic strains did not affect ( P ≥ 0.89) OD, substrate disappearance, or total VFA concentrations, providing further evidence of specificity against fiber-degrading bacteria. Western blotting with anti-FS85 indicated selective binding to F. succinogenes S85 proteins. Identification by LC-MS/MS of 8 selected protein spots indicated 7 were outer membrane proteins. Overall, polyclonal antibodies were more efficacious at inhibiting the growth of targeted cellulolytic bacteria than non-targeted bacteria. Validated polyclonal antibodies could serve as an effective approach to modify rumen bacterial populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tondini, Mackie and McCann.)

Understanding the effects of dosing non-toxigenic Clostridia to cows is rare and has received little attention so far. In the present study, a total of eight lactating dairy cows were divided in two groups: control ( n  = 4) or Clostridia challenged (oral supplementation of five diverse strains of Paraclostridium bifermentans , n  = 4). Bacterial communities were analyzed by qPCR and next-generation sequencing (NGS) in the buccal mucosa as well as digesta and mucosal samples of the gastrointestinal (GI) tract from rumen to rectum (10 compartments), as well as fecal samples. Transcriptomic analysis of barrier and immune-related gene expression was performed on rumen, jejunum, and liver samples. We observed increased microbial populations with the Clostridial challenge in the buccal tissues and the proximal GI tract (forestomach), correlating with Clostridial loads in the feed. Otherwise, there were no significant differences in microbial populations ( p  > 0.05) throughout the distal part of the GI tract. The NGS approach, however, revealed that the Clostridial challenge changed the relative abundance of gut and fecal microbiota. In particular, in the challenge group, no Bifidobacterium was observed in the mucosa-associated microbiota and abundance of Pseudomonadota increased in the feces. These results indicated potential adverse effects of Clostridia to cow health. In general, immune responses to the Clostridial challenge were weak. However, transcriptional analysis revealed the down-regulation of junction adhesion molecule encoding gene (-1.44 of log 2 fold-change), which might impact intestinal permeability., Competing Interests: Authors JT, MJ, JR, TR, and AS were employed by Arm & Hammer Animal and Food Production. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Kim, Thompson, de Jesus, Rehberger, Rehberger, Smith and Mackie.)

To sequester prokaryotic cells in a biofilm-like niche, the creation of a pertinent and reliable microenvironment that reflects the heterogeneous nature of biological systems is vital for sustenance. Design of a microenvironment that is conducive for growth and survival of organisms, should account for factors such as mass transport, porosity, stability, elasticity, size, functionality, and biochemical characteristics of the organisms in the confined architecture. In this work we present an artificial long-term confinement model fabricated by natural alginate hydrogels that are structurally stable and can host organisms for over 10 days in physiologically relevant conditions. A unique feature of the confinement platform is the development of stratified habitats wherein bacterial cells can be entrapped in the core as well as in the shell layers, wherein the thickness and the number of shell layers are tunable at fabrication. We show that the hydrogel microenvironment in the beads can host complex subpopulations of organisms similar to that in a biofilm. Dynamic interaction of bacterial colonies encapsulated in different beads or within the core and stratified layers of single beads was demonstrated to show intra- species communication. Inter- species communication between probiotic bacteria and human colorectal carcinoma cells was also demonstrated to highlight a possible bidirectional communication between the organisms in the beads and the environment. STATEMENT OF SIGNIFICANCE: Bacteria confinement in a natural soft hydrogel structure has always been a challenge due to the collapse of hydrogel architectures. Alternative methods have been attempted to encapsulate microorganisms by employing various processes to avoid/minimize rupturing of hydrogel structures. However, most of the past approaches have been unfavorable in balancing cell proliferation and functionality upon confinement. Our study addresses the fundamental gap in knowledge necessary to create favorable and complex 3D biofilm mimics utilizing natural hydrogel for microbial colonization for long-term studies. Our approach represents a cornerstone in the development of 3D functional architectures not only to advance studies in microbial communication, host-microbe interaction but also to address basic and fundamental questions in biology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Fully understanding the dynamic distribution of the gut microbiota in pigs is essential, as gut microorganisms play a fundamental role in physiological processes, immunity, and the metabolism of nutrients by the host. Here, we first summarize the characteristics and the dynamic shifts in the gut microbial community of pigs at different ages based on the results of 63 peer-review publications. Then a meta-analysis based on the sequences from 16 studies with accession numbers in the GenBank database is conducted to verify the characteristics of the gut microbiota in healthy pigs. A dynamic shift is confirmed in the gut microbiota of pigs at different ages and growth phases. In general, Bacteroides , Escherichia, Clostridium , Lactobacillus , Fusobacterium , and Prevotella are dominant in piglets before weaning, then Prevotella and Aneriacter shift to be the predominant genera with Fusobacterium , Lactobacillus , and Miscellaneous as comparative minors in postweaned pigs. A number of 19 bacterial genera, including Bacteroides , Prevotella , and Lactobacillus can be found in more than 90% of pigs and three enterotypes can be identified in all pigs at different ages, suggesting there is a "core" microbiota in the gut of healthy pigs, which can be a potential target for nutrition or health regulation. The "core" members benefit the growth and gut health of the host. These findings help to define an "optimal" gut microbial profile for assessing, or improving, the performance and health status of pigs at different growth stages. IMPORTANCE The ban on feed antibiotics by more and more countries, and the expected ban on ZnO in feed supplementation from 2022 in the EU, urge researchers and pig producers to search for new alternatives. One possible alternative is to use the so-called "next-generation probiotics (NGPs)" derived from gastrointestinal tract. In this paper, we reveal that a total of 19 "core" bacterial genera including Bacteroides , Prevotella , and Lactobacillus etc., can be found in more than 90% of healthy pigs across different ages. These identified genera may probably be the potential candidates of NGPs or the potential target of microflora regulation. Adding substrates preferred by these target microbes will help to increase the abundance of specific symbiotic species and benefit the gut health of pigs. Further research targeting these "core" microbes and the dynamic distribution of microbiota, as well as the related function is of great importance in swine production.

Anthocyanin-rich strawberry model solutions were co-pigmented with rooibos phenolics to enhance color and heat stability. The addition of green and fermented rooibos extracts at pigment-to-co-pigment molar ratios of 1:10, 1:50, and 1:100 pelargonidin-3-glucoside equivalents: orientin equivalents induced hyper- and bathochromic shifts at room temperature and during thermal processing at 80 °C for an hour. Co-pigmentation effects on hyperchromic shift were up to 96%, and bathochromic shift reached 19 nm when adding flavonoid-rich fractions of green rooibos phenolics. Following the co-pigmentation tests with rooibos extracts, selected pure phenolic co-pigments were tested for their monomeric contribution to the observed co-pigmentation effects. Orientin was identified as a potent co-pigment for pelargonidin-3-glucoside, showing stronger co-pigmentation effects than that of its aglycon luteolin. Additionally, orientin had the most pronounced bathochromic shift in heat-treated solutions. Rooibos extracts, particularly flavonoid-rich fractions composed of luteolin, apigenin, and quercetin glycosides, are suggested as color enhancers and stabilizers for strawberry products., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules. Herein, we describe our work to include felines and feline oral squamous cell carcinoma (FOSCC) patients in the preclinical assessment process to prioritize lead compounds with increased tolerability and efficacy prior to full human translation. Specifically, our data demonstrate that IB-DNQ, an NQO1-targeted small molecule, is well-tolerated in FOSCC patients and shows promising initial efficacy against FOSCC tumors in proof-of-concept single agent and radiotherapy combination cohorts. Furthermore, FOSCC tumors are amenable to evaluating a variety of target-inducible couplet hypotheses, evidenced herein with modulation of NQO1 levels with palliative radiotherapy. The use of felines and their naturally-occurring tumors provide an intriguing, often underutilized tool for preclinical drug development for NQO1-targeted approaches and has broader applications for the evaluation of other anticancer strategies., (Copyright © 2021. Published by Elsevier Inc.)

Migratory marine species cross political borders and enter the high seas, where the lack of an effective global management framework for biodiversity leaves them vulnerable to threats. Here, we combine 10,108 tracks from 5775 individual birds at 87 sites with data on breeding population sizes to estimate the relative year-round importance of national jurisdictions and high seas areas for 39 species of albatrosses and large petrels. Populations from every country made extensive use of the high seas, indicating the stake each country has in the management of biodiversity in international waters. We quantified the links among national populations of these threatened seabirds and the regional fisheries management organizations (RFMOs) which regulate fishing in the high seas. This work makes explicit the relative responsibilities that each country and RFMO has for the management of shared biodiversity, providing invaluable information for the conservation and management of migratory species in the marine realm., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

The single stranded RNA virus SARS-CoV-2 has caused a massive addition to the already leading global cause of mortality, viral respiratory tract infections. Characterized by and associated with early and deleteriously enhanced production of pro-inflammatory cytokines by respiratory epithelial cells, severe COVID-19 illness has the potential to inflict acute respiratory distress syndrome and even death. Due to the fast spreading nature of COVID-19 and the current lack of a vaccine or specific pharmaceutical treatments, understanding of viral pathogenesis, behavioral prophylaxis, and mitigation tactics are of great public health concern. This review article outlines the immune response to viral pathogens, and due to the novelty of COVID-19 and the large body of evidence suggesting the respiratory and immune benefits from regular moderate intensity exercise, provides observational and mechanistic evidence from research on other viral infections that suggests strategically planned exercise regimens may help reduce susceptibility to infection, while also mitigating severe immune responses to infection commonly associated with poor COVID-19 prognosis. We propose that regular moderate intensity exercise should be considered as part of a combinatorial approach including widespread hygiene initiatives, properly planned and well-executed social distancing policies, and use of efficacious facial coverings like N95 respirators. Studies discerning COVID-19 pathogenesis mechanisms, transfer dynamics, and individual responses to pharmaceutical and adjunct treatments are needed to reduce viral transmission and bring an end to the COVID-19 pandemic., Competing Interests: The authors declare that they have no competing interests., (© 2020 Chengdu Sport University. Production and hosting by Elsevier B.V. on behalf of KeAi.)

H. pylori infection is one of the leading causes of gastric cancer and the pathogenicity of H. pylori infection is associated with its ability to induce chronic inflammation and apoptosis resistance. While H. pylori infection-induced expression of pro-inflammatory cytokines for chronic inflammation is well studied, the molecular mechanism underlying the apoptosis resistance in infected cells is not well understood. In this study, we demonstrated that H. pylori infection-induced apoptosis resistance in gastric epithelial cells triggered by Raptinal, a drug that directly activates caspase-3. This resistance resulted from the induction of cIAP2 (encoded by BIRC3) since depletion of BIRC3 by siRNA or inhibition of cIAP2 via BV6 reversed H. pylori-suppressed caspase-3 activation. The induction of cIAP2 was regulated by H. pylori-induced BIRC3 eRNA synthesis. Depletion of BIRC3 eRNA decreased H. pylori-induced cIAP2 and reversed H. pylori-suppressed caspase-3 activation. Mechanistically, H. pylori stimulated the recruitment of bromodomain-containing factor Brd4 to the enhancer of BIRC3 and promoted BIRC3 eRNA and mRNA synthesis. Inhibition of Brd4 diminished the expression of BIRC3 eRNA and the anti-apoptotic response to H. pylori infection. Importantly, H. pylori isogenic cagA-deficient mutant failed to activate the synthesis of BIRC3 eRNA and the associated apoptosis resistance. Finally, in primary human gastric epithelial cells, H. pylori also induced resistance to Raptinal-triggered caspase-3 activation by activating the Brd4-dependent BIRC3 eRNA synthesis in a CagA-dependent manner. These results identify a novel function of Brd4 in H. pylori-mediated apoptosis resistance via activating BIRC3 eRNA synthesis, suggesting that Brd4 could be a potential therapeutic target for H. pylori-induced gastric cancer.

Maternal investment directly shapes early developmental conditions and therefore has long-term fitness consequences for the offspring. In oviparous species prenatal maternal investment is fixed at the time of laying. To ensure the best survival chances for most of their offspring, females must equip their eggs with the resources required to perform well under various circumstances, yet the actual mechanisms remain unknown. Here we describe the blue tit egg albumen and yolk proteomes and evaluate their potential to mediate maternal effects. We show that variation in egg composition (proteins, lipids, carotenoids) primarily depends on laying order and female age. Egg proteomic profiles are mainly driven by laying order, and investment in the egg proteome is functionally biased among eggs. Our results suggest that maternal effects on egg composition result from both passive and active (partly compensatory) mechanisms, and that variation in egg composition creates diverse biochemical environments for embryonic development., Competing Interests: During the study, one of the authors (R.M.S.) left the University of Hohenheim to take up a position at a manufacturer of carotenoid supplements (DSM Nutritional Products, Kaiseraugst, Switzerland). The remaining authors declare no competing interests.

A wealth of neuroscience evidence demonstrates that aerobic fitness enhances structural brain plasticity, promoting the development of gray matter volume and maintenance of white matter integrity within networks for executive function, attention, learning, and memory. However, the role of aerobic fitness in shaping the functional brain connectome remains to be established. The present work therefore investigated the effects of aerobic fitness (as measured by VO2max) on individual differences in whole-brain functional connectivity assessed from resting state fMRI data. Using a connectome-wide association study, we identified significant brain-fitness relationships within a large sample of healthy young adults (N = 242). The results revealed several regions within frontal, temporal, parietal, and cerebellar cortex, having significant association with aerobic fitness. We further characterized the influence of these regions on 7 intrinsic connectivity networks, demonstrating the greatest association with networks that are known to mediate the beneficial effects of aerobic fitness on executive function (frontoparietal network), attention and learning (dorsal and ventral attention network), and memory (default mode network). In addition, we provide evidence that connectivity strength between these regions and the frontoparietal network is predictive of individuals' fluid intelligence.

Despite a growing body of research suggesting that task-based functional magnetic resonance imaging (fMRI) studies often suffer from a lack of statistical power due to too-small samples, the proliferation of such underpowered studies continues unabated. Using large independent samples across eleven tasks, we demonstrate the impact of sample size on replicability, assessed at different levels of analysis relevant to fMRI researchers. We find that the degree of replicability for typical sample sizes is modest and that sample sizes much larger than typical (e.g., N  = 100) produce results that fall well short of perfectly replicable. Thus, our results join the existing line of work advocating for larger sample sizes. Moreover, because we test sample sizes over a fairly large range and use intuitive metrics of replicability, our hope is that our results are more understandable and convincing to researchers who may have found previous results advocating for larger samples inaccessible., Competing Interests: The authors declare no competing interests.

While an extensive literature in decision neuroscience has elucidated the neurobiological foundations of decision making, prior research has focused primarily on group-level effects in a sample population. Due to the presence of inherent differences between individuals' cognitive abilities, it is also important to examine the neural correlates of decision making that explain interindividual variability in cognitive performance. This study therefore investigated how individual differences in decision making competence, as measured by the Adult Decision Making Competence (A-DMC) battery, are related to functional brain connectivity patterns derived from resting-state fMRI data in a sample of 304 healthy participants. We examined connectome-wide associations, identifying regions within frontal, parietal, temporal, and occipital cortex that demonstrated significant associations with decision making competence. We then assessed whether the functional interactions between brain regions sensitive to decision making competence and seven intrinsic connectivity networks (ICNs) were predictive of specific facets of decision making assessed by subtests of the A-DMC battery. Our findings suggest that individual differences in specific facets of decision making competence are mediated by ICNs that support executive, social, and perceptual processes, and motivate an integrative framework for understanding the neural basis of individual differences in decision making competence., (© 2018 Wiley Periodicals, Inc.)

Sugar-containing beverages like orange juice can be a risk factor for obesity and type 2 diabetes although the underlying mechanisms are less clear. We aimed to investigate if intake of orange juice with or in-between meals differently affects energy balance or metabolic risk. Twenty-six healthy adults (24.7 ± 3.2 y; BMI 23.2 ± 3.2 kg/m 2 ) participated in a 4-week cross-over intervention and consumed orange juice (20% of energy requirement) either together with 3 meals/d (WM) or in-between 3 meals/d (BM) at ad libitum energy intake. Basal and postprandial insulin sensitivity (primary outcome), daylong glycaemia, glucose variability and insulin secretion were assessed. Body fat mass was measured by air-displacement plethysmography. After BM-intervention, fat mass increased (+1.0 ± 1.8 kg; p < 0.05) and postprandial insulin sensitivity tended to decrease (ΔMatsuda ISI : -0.89 ± 2.3; p = 0.06). By contrast, after WM-intervention fat mass and gamma-glutamyl transferase (GGT) decreased (-0.30 ± 0.65 kg; -2.50 ± 3.94; both p < 0.05), whereas glucose variability was higher (ΔMAGE: +0.45 ± 0.59, p < 0.05). Daylong glycaemia, insulin secretion, changes in basal insulin sensitivity, and triglycerides did not differ between WM- and BM-interventions (all p > 0.05). In young healthy adults, a conventional 3-meal structure with orange juice consumed together with meals had a favorable impact on energy balance, whereas juice consumption in-between meals may contribute to a gain in body fat and adverse metabolic effects.

Despite broad agreement that the Americas were initially populated via Beringia, the land bridge that connected far northeast Asia with northwestern North America during the Pleistocene epoch, when and how the peopling of the Americas occurred remains unresolved. Analyses of human remains from Late Pleistocene Alaska are important to resolving the timing and dispersal of these populations. The remains of two infants were recovered at Upward Sun River (USR), and have been dated to around 11.5 thousand years ago (ka). Here, by sequencing the USR1 genome to an average coverage of approximately 17 times, we show that USR1 is most closely related to Native Americans, but falls basal to all previously sequenced contemporary and ancient Native Americans. As such, USR1 represents a distinct Ancient Beringian population. Using demographic modelling, we infer that the Ancient Beringian population and ancestors of other Native Americans descended from a single founding population that initially split from East Asians around 36 ± 1.5 ka, with gene flow persisting until around 25 ± 1.1 ka. Gene flow from ancient north Eurasians into all Native Americans took place 25-20 ka, with Ancient Beringians branching off around 22-18.1 ka. Our findings support a long-term genetic structure in ancestral Native Americans, consistent with the Beringian 'standstill model'. We show that the basal northern and southern Native American branches, to which all other Native Americans belong, diverged around 17.5-14.6 ka, and that this probably occurred south of the North American ice sheets. We also show that after 11.5 ka, some of the northern Native American populations received gene flow from a Siberian population most closely related to Koryaks, but not Palaeo-Eskimos, Inuits or Kets, and that Native American gene flow into Inuits was through northern and not southern Native American groups. Our findings further suggest that the far-northern North American presence of northern Native Americans is from a back migration that replaced or absorbed the initial founding population of Ancient Beringians.

Carotenoid bioavailability from plant and animal food is highly variable depending on numerous factors such as the physical deposition form of carotenoids. As the carotenoid zeaxanthin is believed to play an important role in eye and brain health, we sought to compare the human bioavailability of an H-aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated into identical formulation matrices. A randomised two-way cross-over study with sixteen participants was designed to compare the post-prandial bioavailability of an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation, both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich lipoprotein fractions were analysed over 9·5 h after test meal consumption. Bioavailability from the J-aggregated formulation (AUC=55·9 nmol h/l) was 23 % higher than from the H-aggregated one (AUC=45·5 nmol h/l), although being only marginally significant (P=0·064). Furthermore, the same formulations were subjected to an internationally recognised in vitro digestion protocol to reveal potential strengths and weaknesses of simulated digestions. In agreement with our human study, liberation of zeaxanthin from the J-aggregated formulation into the simulated duodenal fluids was superior to that from the H-aggregated form. However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin dipalmitate was lower than that of the H-aggregated zeaxanthin, being contradictory to our in vivo results. An insufficient ester cleavage during simulated digestion was suggested to be the root cause for these observations. In brief, combining our in vitro and in vivo observations, the effect of the different aggregation forms on human bioavailability was lower than expected.

The potential impact of brain training methods for enhancing human cognition in healthy and clinical populations has motivated increasing public interest and scientific scrutiny. At issue is the merits of intervention modalities, such as computer-based cognitive training, physical exercise training, and non-invasive brain stimulation, and whether such interventions synergistically enhance cognition. To investigate this issue, we conducted a comprehensive 4-month randomized controlled trial in which 318 healthy, young adults were enrolled in one of five interventions: (1) Computer-based cognitive training on six adaptive tests of executive function; (2) Cognitive and physical exercise training; (3) Cognitive training combined with non-invasive brain stimulation and physical exercise training; (4) Active control training in adaptive visual search and change detection tasks; and (5) Passive control. Our findings demonstrate that multimodal training significantly enhanced learning (relative to computer-based cognitive training alone) and provided an effective method to promote skill learning across multiple cognitive domains, spanning executive functions, working memory, and planning and problem solving. These results help to establish the beneficial effects of multimodal intervention and identify key areas for future research in the continued effort to improve human cognition.

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.