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Showing papers on "B vitamins published in 2017"


Journal ArticleDOI
10 Aug 2017-Cell
TL;DR: The molecular organization of several B-specific proteins suggests that they are involved in negatively regulating Brr2, positioning the U6/5'ss helix, and stabilizing the B complex structure.

194 citations


Journal ArticleDOI
29 Jun 2017-Nature
TL;DR: The cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae pre-catalytic B complex spliceosome at near-atomic resolution is reported, providing important insights into the events leading to active site formation.
Abstract: Intron removal requires assembly of the spliceosome on precursor mRNA (pre-mRNA) and extensive remodelling to form the spliceosome's catalytic centre. Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae pre-catalytic B complex spliceosome at near-atomic resolution. The mobile U2 small nuclear ribonucleoprotein particle (snRNP) associates with U4/U6.U5 tri-snRNP through the U2/U6 helix II and an interface between U4/U6 di-snRNP and the U2 snRNP SF3b-containing domain, which also transiently contacts the helicase Brr2. The 3' region of the U2 snRNP is flexibly attached to the SF3b-containing domain and protrudes over the concave surface of tri-snRNP, where the U1 snRNP may reside before its release from the pre-mRNA 5' splice site. The U6 ACAGAGA sequence forms a hairpin that weakly tethers the 5' splice site. The B complex proteins Prp38, Snu23 and Spp381 bind the Prp8 N-terminal domain and stabilize U6 ACAGAGA stem-pre-mRNA and Brr2-U4 small nuclear RNA interactions. These results provide important insights into the events leading to active site formation.

187 citations


Journal ArticleDOI
TL;DR: Examination of 81 tick species shows that some Coxiella‐LE symbioses are evolutionarily stable with an ancient acquisition followed by codiversification as observed in ticks belonging to the Rhipicephalus genus, however, many other Coxiellas-LE symbionts are characterized by low evolutionary stability with frequent host shifts and extinction events.
Abstract: Ecological specialization to restricted diet niches is driven by obligate, and often maternally inherited, symbionts in many arthropod lineages. These heritable symbionts typically form evolutionarily stable associations with arthropods that can last for millions of years. Ticks were recently found to harbour such an obligate symbiont, Coxiella-LE, that synthesizes B vitamins and cofactors not obtained in sufficient quantities from blood diet. In this study, the examination of 81 tick species shows that some Coxiella-LE symbioses are evolutionarily stable with an ancient acquisition followed by codiversification as observed in ticks belonging to the Rhipicephalus genus. However, many other Coxiella-LE symbioses are characterized by low evolutionary stability with frequent host shifts and extinction events. Further examination revealed the presence of nine other genera of maternally inherited bacteria in ticks. Although these nine symbionts were primarily thought to be facultative, their distribution among tick species rather suggests that at least four may have independently replaced Coxiella-LE and likely represent alternative obligate symbionts. Phylogenetic evidence otherwise indicates that cocladogenesis is globally rare in these symbioses as most originate via horizontal transfer of an existing symbiont between unrelated tick species. As a result, the structure of these symbiont communities is not fixed and stable across the tick phylogeny. Most importantly, the symbiont communities commonly reach high levels of diversity with up to six unrelated maternally inherited bacteria coexisting within host species. We further conjecture that interactions among coexisting symbionts are pivotal drivers of community structure both among and within tick species.

165 citations


Journal ArticleDOI
TL;DR: Cohort Profile: The Melbourne Collaborative Cohort Study (Health 2020) R L Milne,* A S Fletcher, R J MacInnis, A M Hodge, A H Hopkins, J K Bassett, F J Bruinsma, and P A Dugué.
Abstract: Cohort Profile: The Melbourne Collaborative Cohort Study (Health 2020) R L Milne,* A S Fletcher, R J MacInnis, A M Hodge, A H Hopkins, J K Bassett, F J Bruinsma, B M Lynch, P A Dugué, H Jayasekara, M T Brinkman, L V Popowski, L Baglietto, G Severi, K O’Dea, J L Hopper, M C Southey, D R English and G G Giles Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, Australia, Physical Activity Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia, Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Saclay, Villejuif, France, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, Human Genetics Foundation (HuGeF), Turin, Italy, Centre of Population Health Research, University of South Australia, Adelaide, SA, Australia and Genetic Epidemiology Laboratory, University of Melbourne, Parkville, VIC, Australia

114 citations


Journal ArticleDOI
TL;DR: The current evidence suggests that the dietary intake of most food pantry users does not meet recommendations.

108 citations


Journal ArticleDOI
TL;DR: The epigenetic effects of air pollution are demonstrated and individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM2.5 effects, with possible significant public health benefit in areas with frequent PM 2.5 peaks.
Abstract: Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4+ T-helper cells. PM2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5 depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; P = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM2.5 effect by 102% (Pinteraction = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM2.5 effects, with possible significant public health benefit in areas with frequent PM2.5 peaks.

107 citations


Journal ArticleDOI
TL;DR: Knowing how immune cells change in the presence of vitamin B derivatives could improve understanding of how immune changes may correlate with depression, all of which are discussed herein.

93 citations


Journal ArticleDOI
TL;DR: The meta-analysis of individual patient data from two large trials of B vitamin therapy indicates that patients with impaired renal function who are exposed to high-dose cyanocobalamin do not benefit from therapy with B vitamins for the prevention of stroke.
Abstract: Summary B vitamin therapy lowers plasma total homocysteine concentrations, and might be a beneficial intervention for stroke prevention; however, cyanocobalamin (a form of vitamin B12) can accelerate decline in renal function and increase the risk of cardiovascular events in patients with impaired renal function. Although early trials did not show benefit in reduction of stroke, these results might have been due to harm in participants with impaired renal function. In patients with diabetic nephropathy, cyanocobalamin is harmful, whereas B vitamins appear to reduce cardiovascular events in study participants with normal renal function. Our meta-analysis of individual patient data from two large trials of B vitamin therapy (VISP and VITATOPS) indicates that patients with impaired renal function who are exposed to high-dose cyanocobalamin do not benefit from therapy with B vitamins for the prevention of stroke (risk ratio 1·04, 95% CI 0·84–1·27), however, patients with normal renal function who are not exposed to high-dose cyanocobalamin benefit significantly from this treatment (0.78, 0·67–0·90; interaction p=0·03). The potential benefits of B vitamin therapy with folic acid and methylcobalamin or hydroxycobalamin, instead of cyanocobalamin, to lower homocysteine concentrations in people at high risk of stroke warrant further investigation.

91 citations


Journal ArticleDOI
26 Sep 2017-Mbio
TL;DR: The reconstructed metabolic network offers clues to how rickettsiae hijack host metabolic pathways to counterbalance numerous disintegrated biosynthesis pathways that have arisen through evolution within the eukaryotic cell.
Abstract: Reductive genome evolution has purged many metabolic pathways from obligate intracellular Rickettsia (Alphaproteobacteria; Rickettsiaceae) While some aspects of host-dependent rickettsial metabolism have been characterized, the array of host-acquired metabolites and their cognate transporters remains unknown This dearth of information has thwarted efforts to obtain an axenic Rickettsia culture, a major impediment to conventional genetic approaches Using phylogenomics and computational pathway analysis, we reconstructed the Rickettsia metabolic and transport network, identifying 51 host-acquired metabolites (only 21 previously characterized) needed to compensate for degraded biosynthesis pathways In the absence of glycolysis and the pentose phosphate pathway, cell envelope glycoconjugates are synthesized from three imported host sugars, with a range of additional host-acquired metabolites fueling the tricarboxylic acid cycle Fatty acid and glycerophospholipid pathways also initiate from host precursors, and import of both isoprenes and terpenoids is required for the synthesis of ubiquinone and the lipid carrier of lipid I and O-antigen Unlike metabolite-provisioning bacterial symbionts of arthropods, rickettsiae cannot synthesize B vitamins or most other cofactors, accentuating their parasitic nature Six biosynthesis pathways contain holes (missing enzymes); similar patterns in taxonomically diverse bacteria suggest alternative enzymes that await discovery A paucity of characterized and predicted transporters emphasizes the knowledge gap concerning how rickettsiae import host metabolites, some of which are large and not known to be transported by bacteria Collectively, our reconstructed metabolic network offers clues to how rickettsiae hijack host metabolic pathways This blueprint for growth determinants is an important step toward the design of axenic media to rescue rickettsiae from the eukaryotic cellIMPORTANCE A hallmark of obligate intracellular bacteria is the tradeoff of metabolic genes for the ability to acquire host metabolites For species of Rickettsia, arthropod-borne parasites with the potential to cause serious human disease, the range of pilfered host metabolites is unknown This information is critical for dissociating rickettsiae from eukaryotic cells to facilitate rickettsial genetic manipulation In this study, we reconstructed the Rickettsia metabolic network and identified 51 host metabolites required to compensate patchwork Rickettsia biosynthesis pathways Remarkably, some metabolites are not known to be transported by any bacteria, and overall, few cognate transporters were identified Several pathways contain missing enzymes, yet similar pathways in unrelated bacteria indicate convergence and possible novel enzymes awaiting characterization Our work illuminates the parasitic nature by which rickettsiae hijack host metabolism to counterbalance numerous disintegrated biosynthesis pathways that have arisen through evolution within the eukaryotic cell This metabolic blueprint reveals what a Rickettsia axenic medium might entail

90 citations


Journal ArticleDOI
TL;DR: Taking together, vitamin B supplementation was effective in reducing serum homocysteine levels, however, it did not translate into cognitive improvement, indicating that the existing data on vitamin B-induced improvement in cognition by lowering homocy steine levels are conflicting.
Abstract: Increase in serum homocysteine is shown to be a potential risk factor for cognitive impairment. Evidence suggests that vitamin B supplementation may reduce cognitive decline by lowering the homocysteine levels. The current meta-analysis evaluated the efficacy of folic acid along with vitamin B12 and/or B6 in lowering homocysteine, thereby attenuating cognitive decline in elderly patients with Alzheimer disease or dementia. Randomized controlled trials (RCTs) comparing the efficacy of folate and B vitamin supplementation in patients with cognitive decline secondary to Alzheimer disease or dementia were identified using the keywords, "homocysteine, hyper-homocysteinemia, B vitamin, vitamin B6, B12, folic acid, cognitive, Alzheimer's disease, and dementia." The outcome measures analyzed were the Mini-Mental State Examination (MMSE) score and serum homocysteine. Of the 77 studies identified, 4 RCTs were included in the current meta-analysis. The baseline characteristics, age, and gender distribution of patients among the 2 groups (supplement vs placebo) were comparable. The results reveal that the intervention group achieved significantly greater reduction in homocysteine levels than the control (pooled difference in means = -3.625, 95% confidence interval [CI] = -5.642 to -1.608, P < .001). However, no significant difference in MMSE (pooled difference in means = 0.027, 95% CI = -0.518 to 0.573, P = 0.921) was observed between the groups. Taken together, vitamin B supplementation was effective in reducing serum homocysteine levels. However, it did not translate into cognitive improvement, indicating that the existing data on vitamin B-induced improvement in cognition by lowering homocysteine levels are conflicting.

84 citations


Journal ArticleDOI
TL;DR: Nuts could make a valuable contribution to a healthy diet in regard to B-vitamins, lutein/zeaxanthin and tocopherols as well as a reduction in micronutrient content by roasting.

Journal ArticleDOI
TL;DR: This review will be a valuable resource for more studies on rice barn as a dietary source and reported that potent antioxidants in rice bran included immune system enhancing compounds, such as phytosterols, polysaccharides, minerals and trace minerals.
Abstract: Rice bran, one of the most abundant and valuable byproducts produced during the rice milling process, is of steadily growing interest in recent years due to its potential health benefits. Evidence is rapidly accumulating for the beneficial effects of nutraceuticals. However, the potential benefits of rice bran are found in several of its bioactive ingredients including oils, polysaccharides, proteins, and micronutrients. In addition, a significant advantage of rice bran is that it contains more than 100 antioxidants and several categories of bioactive phytonutrients, such as polyphenols, phytosterols, tocotrienols, γ-oryzanol, B vitamins, minerals, and trace minerals. As an immunomodulator, rice bran has beneficial constituents such as polysaccharides, proteins, and oils. Numerous studies also reported that potent antioxidants in rice bran included immune system enhancing compounds, such as phytosterols, polysaccharides, minerals and trace minerals including magnesium, selenium, zinc, vitamin E, omega-3 fatty acids and several other phytonutrients. We believe that this review will be a valuable resource for more studies on rice barn as a dietary source.

Journal ArticleDOI
TL;DR: Insects generally cannot synthesize eight B vitamins that function as co-enzymes in various required enzymatic reactions, but the genomes of a few insects bear genes in vitamin B5 (pantothenate) and B7 (biotin) synthesis, horizontally acquired from bacteria.
Abstract: Insects generally cannot synthesize eight B vitamins that function as co-enzymes in various required enzymatic reactions. Most insects derive their B vitamin requirements from the diet, microbial symbionts, or a combination of these complementary sources. Exceptionally, the genomes of a few insects bear genes in vitamin B5 (pantothenate) and B7 (biotin) synthesis, horizontally acquired from bacteria. Biomarkers of B vitamin deficiency (e.g. vitamin titers, activity of vitamin-dependent enzymes) offer routes to investigate the incidence and the physiological and fitness consequences of B vitamin deficiency in laboratory and field populations of insects.

Journal ArticleDOI
TL;DR: A point mutation of RABL2 found in sperm motility–defective mice abolishes its binding to IFT-B but not to CEP19, suggesting a crucial role of RabL2 in ciliary assembly.
Abstract: Proteins localized to the basal body and the centrosome play crucial roles in ciliary assembly and function. Although RABL2 and CEP19 are conserved in ciliated organisms and have been implicated in ciliary/flagellar functions, their roles are poorly understood. Here we show that RABL2 interacts with CEP19 and is recruited to the mother centriole and basal body in a CEP19-dependent manner and that CEP19 is recruited to the centriole probably via its binding to the centrosomal protein FGFR1OP. Disruption of the RABL2 gene in Chlamydomonas reinhardtii results in the nonflagellated phenotype, suggesting a crucial role of RABL2 in ciliary/flagellar assembly. We also show that RABL2 interacts, in its GTP-bound state, with the intraflagellar transport (IFT)-B complex via the IFT74-IFT81 heterodimer and that the interaction is disrupted by a mutation found in male infertile mice (Mot mice) with a sperm flagella motility defect. Intriguingly, RABL2 binds to CEP19 and the IFT74-IFT81 heterodimer in a mutually exclusive manner. Furthermore, exogenous expression of the GDP-locked or Mot-type RABL2 mutant in human cells results in mild defects in ciliary assembly. These results indicate that RABL2 localized to the basal body plays crucial roles in ciliary/flagellar assembly via its interaction with the IFT-B complex.

Journal ArticleDOI
TL;DR: The evidence on whether nutritional factors influence the risk of perinatal depression is still inconclusive, and further longitudinal studies are needed, with robust and consistent measurement of dietary intake and depressive symptoms, ideally starting before pregnancy.
Abstract: This article presents a systematic literature review on whether dietary intake influences the risk for perinatal depression, i.e. depression during pregnancy or post-partum. Such a link has been hypothesized given that certain nutrients are important in the neurotransmission system and pregnancy depletes essential nutrients. PubMed, EMBASE and CINAHL databases were searched for relevant articles until 30 May 2015. We included peer-reviewed studies of any design that evaluated whether perinatal depression is related to dietary intake, which was defined as adherence to certain diets, food-derived intake of essential nutrients or supplements. We identified 4808 studies, of which 35 fulfilled inclusion criteria: six randomized controlled trials, 12 cohort, one case-control and 16 cross-sectional studies, representing 88 051 distinct subjects. Studies were grouped into four main categories based on the analysis of dietary intake: adherence to dietary patterns (nine studies); full panel of essential nutrients (six studies); specific nutrients (including B vitamins, Vitamin D, calcium and zinc; eight studies); and intake of fish or polyunsaturated fatty acids (PUFAs; 12 studies). While 13 studies, including three PUFA supplementation trials, found no evidence of an association, 22 studies showed protective effects from healthy dietary patterns, multivitamin supplementation, fish and PUFA intake, calcium, Vitamin D, zinc and possibly selenium. Given the methodological limitations of existing studies and inconsistencies in findings across studies, the evidence on whether nutritional factors influence the risk of perinatal depression is still inconclusive. Further longitudinal studies are needed, with robust and consistent measurement of dietary intake and depressive symptoms, ideally starting before pregnancy.

Journal ArticleDOI
TL;DR: The results indicate that plant driven nutrient patterns are associated with low fasting glucose and glycated haemoglobin levels, similar to other type 2 diabetes biomarkers.
Abstract: Type 2 diabetes (T2D) burden is increasing globally. However, evidence regarding nutrient patterns associated with the biomarkers of T2D is limited. This study set out to determine the nutrient patterns associated with fasting glucose and glycated haemoglobin the biomarkers of T2D. Factor analysis was used to derive nutrient patterns of 2010 participants stratified by urban/rural status and gender. Principal Component Analysis (PCA) was applied to 25 nutrients, computed from the quantified food frequency questionnaires (QFFQ). Three nutrient patterns per stratum, which accounted for 73% of the variation of the selected nutrients, were identified. Multivariate linear regression models adjusted for age, BMI, smoking, physical activity, education attained, alcohol intake, seasonality and total energy intake were computed. Starch, dietary fibre and B vitamins driven nutrient pattern was significantly associated with fasting glucose (β = −0.236 (−0.458; −0.014); p = 0.037) and glycated haemoglobin levels (β = −0.175 (−0.303; −0.047); p = 0.007) in rural women. Thiamine, zinc and plant protein driven nutrient pattern was associated with significant reductions in glycated haemoglobin and fasting glucose ((β = −0.288 (−0.543; −0.033); p = 0.027) and (β = −0.382 (−0.752; −0.012); p = 0.043), respectively) in rural men. Our results indicate that plant driven nutrient patterns are associated with low fasting glucose and glycated haemoglobin levels.

Journal ArticleDOI
TL;DR: Preliminary evidence is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population of schizophrenia.
Abstract: Background When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways. Method We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments. Results An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [g = 0.508, 95% confidence interval (CI) 0.01–1.01, p = 0.047, I 2 = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses (g = 0.734, 95% CI 0.00–1.49, p = 0.051). However, no effects of B vitamins were observed in individual domains of positive and negative symptoms (both p > 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness (p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms. Conclusions There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas.

Journal ArticleDOI
TL;DR: This sex- and source-specific association provides further evidence that vitamin B supplements are not chemopreventive for lung cancer and may be harmful.
Abstract: PurposeInconsistent findings have been reported of a link between the use of one-carbon metabolism–related B vitamins and lung cancer risk. Because of the high prevalence of supplemental vitamin B use, any possible increased association warrants further investigation. We examined the association between long-term use of supplemental B vitamins on the one-carbon metabolism pathway and lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort, which was designed specifically to look at supplement use relative to cancer risk.MethodsA total of 77,118 participants of the VITAL cohort, 50 to 76 years of age, were recruited between October 2000 and December 2002 and included in this analysis. Incident, primary, invasive lung cancers (n = 808) were ascertained by prospectively linking the participants to a population-based cancer registry. The 10-year average daily dose from individual and multivitamin supplements were the exposures of primary interest.ResultsUse of supplemental vitamins B6, folate, and B12 w...

Journal ArticleDOI
TL;DR: In this article, the functional composition and antioxidant activities of eight major date fruit varieties grown in Morocco were analyzed and found that date fruit contains a high amount of sugar (6603-8305% DW) but a low content of fat (0218-0363%) and protein (22-345% DW).

Journal ArticleDOI
TL;DR: Recent advances in algal genetic resources and environmental chemistry are described and how they redefine the view of the way in which vitamins are cycled in aquatic ecosystems and their importance in structuring phytoplankton communities are discussed.
Abstract: Contents 62 I. 62 II. 63 III. 63 IV. 66 V. 66 VI. 67 67 References 67 SUMMARY: B vitamins play essential roles in central metabolism. These organic water-soluble molecules act as, or as part of, coenzymes within the cell. Unlike land plants, many eukaryotic algae are auxotrophic for certain B vitamins. Recent progress in algal genetic resources and environmental chemistry have promoted a renewal of interest in the role of vitamins in governing phytoplankton dynamics, and illuminated amazing versatility in phytoplankton vitamin metabolism. Accumulating evidence demonstrates metabolic complexity in the production and bioavailability of different vitamin forms, coupled with specialized acquisition strategies to salvage and remodel vitamin precursors. Here, I describe recent advances and discuss how they redefine our view of the way in which vitamins are cycled in aquatic ecosystems and their importance in structuring phytoplankton communities.

Journal ArticleDOI
TL;DR: The differences in bioavailability and metabolism of synthetic folic acid and natural dietary folate as well as variation in the baseline characteristics of subjects and various methods of folate status assessment might be the main reasons for these controversies.

Journal ArticleDOI
TL;DR: To decipher the core functions of this symbiosis essential for tsetse's survival, dual-RNA-seq analysis of the bacteriome was performed, coupled with metabolomic analysis of bacteriomes and haemolymph collected from normal and symbiont-cured (sterile) females.
Abstract: Insects with restricted diets rely on obligate microbes to fulfil nutritional requirements essential for biological function. Tsetse flies, vectors of African trypanosome parasites, feed exclusively on vertebrate blood and harbour the obligate endosymbiont Wigglesworthia glossinidia. Without Wigglesworthia, tsetse are unable to reproduce. These symbionts are sheltered within specialized cells (bacteriocytes) that form the midgut-associated bacteriome organ. To decipher the core functions of this symbiosis essential for tsetse's survival, we performed dual-RNA-seq analysis of the bacteriome, coupled with metabolomic analysis of bacteriome and haemolymph collected from normal and symbiont-cured (sterile) females. Bacteriocytes produce immune regulatory peptidoglycan recognition protein (pgrp-lb) that protects Wigglesworthia, and a multivitamin transporter (smvt) that can aid in nutrient dissemination. Wigglesworthia overexpress a molecular chaperone (GroEL) to augment their translational/transport machinery and biosynthesize an abundance of B vitamins (specifically B1-, B2-, B3- and B6-associated metabolites) to supplement the host's nutritionally deficient diet. The absence of Wigglesworthia's contributions disrupts multiple metabolic pathways impacting carbohydrate and amino acid metabolism. These disruptions affect the dependent downstream processes of nucleotide biosynthesis and metabolism and biosynthesis of S-adenosyl methionine (SAM), an essential cofactor. This holistic fundamental knowledge of the symbiotic dialogue highlights new biological targets for the development of innovative vector control methods.

Journal ArticleDOI
TL;DR: The three-compartment model of metabolic flux between two bacterial symbionts and their insect host revealed that one symbiont is structured to overproduce essential amino acids for the benefit of the host, but the essential amino acid production in the second symbionT is quantitatively constrained by the structure of its network, rendering it “selfish” with respect to these nutrients.
Abstract: An important factor determining the impact of microbial symbionts on their animal hosts is the balance between the cost of nutrients consumed by the symbionts and the benefit of nutrients released back to the host, but the quantitative significance of nutrient exchange in symbioses involving multiple microbial partners has rarely been addressed. In this study on the association between two intracellular bacterial symbionts, "Candidatus Portiera aleyrodidarum" and "Candidatus Hamiltonella defensa," and their animal host, the whitefly Bemisia tabaci, we apply metabolic modeling to investigate host-symbiont nutrient exchange. Our in silico analysis revealed that >60% of the essential amino acids and related metabolites synthesized by "Candidatus Portiera aleyrodidarum" are utilized by the host, including a substantial contribution of nitrogen recycled from host nitrogenous waste, and that these interactions are required for host growth. In contrast, "Candidatus Hamiltonella defensa" retains most or all of the essential amino acids and B vitamins that it is capable of synthesizing. Furthermore, "Candidatus Hamiltonella defensa" suppresses host growth in silico by competition with "Candidatus Portiera aleyrodidarum" for multiple host nutrients, by suppressing "Candidatus Portiera aleyrodidarum" growth and metabolic function, and also by consumption of host nutrients that would otherwise be allocated to host growth. The interpretation from these modeling outputs that "Candidatus Hamiltonella defensa" is a nutritional parasite could not be inferred reliably from gene content alone but requires consideration of constraints imposed by the structure of the metabolic network. Furthermore, these quantitative models offer precise predictions for future experimental study and the opportunity to compare the functional organization of metabolic networks in different symbioses.IMPORTANCE The metabolic functions of unculturable intracellular bacteria with much reduced genomes are traditionally inferred from gene content without consideration of how the structure of the metabolic network may influence flux through metabolic reactions. The three-compartment model of metabolic flux between two bacterial symbionts and their insect host constructed in this study revealed that one symbiont is structured to overproduce essential amino acids for the benefit of the host, but the essential amino acid production in the second symbiont is quantitatively constrained by the structure of its network, rendering it "selfish" with respect to these nutrients. This study demonstrates the importance of quantitative flux data for elucidation of the metabolic function of symbionts. The in silico methodology can be applied to other symbioses with intracellular bacteria.

Journal ArticleDOI
TL;DR: Evaluated studies and literature that address the status and supplementation of omega‐3 polyunsaturated fatty acids, vitamin D, B vitamins, vitamin E, and carotenoids in different stages of schizophrenia find possible anti‐inflammatory and antioxidant mechanisms of action.
Abstract: Over 50 million people around the world suffer from schizophrenia, a severe mental illness characterized by misinterpretation of reality. Although the exact causes of schizophrenia are still unknown, studies have indicated that inflammation and oxidative stress may play an important role in the etiology of the disease. Pro-inflammatory cytokines are crucial for normal central nervous development and proper functioning of neural networks and neurotransmitters. Patients with schizophrenia tend to have abnormal immune activation resulting in elevated pro-inflammatory cytokine levels, ultimately leading to functional brain impairments. Patients with schizophrenia have also been found to suffer from oxidative stress, a result of an imbalance between the production of free radicals and the ability to detoxify their harmful effects. Furthermore, inflammation and oxidative stress are implicated to be related to the severity of psychotic symptoms. Several nutrients are known to have anti-inflammatory and antioxidant functions through various mechanisms in our body. The present review evaluates studies and literature that address the status and supplementation of omega-3 polyunsaturated fatty acids, vitamin D, B vitamins (B6, folate, B12), vitamin E, and carotenoids in different stages of schizophrenia. The possible anti-inflammatory and antioxidant mechanisms of action of each nutrient are discussed.

Journal ArticleDOI
TL;DR: Although a necessity in proper management of GRDs, unforeseen nutritional complications may develop in patients who are gluten free for which enhanced physician awareness is vital to achieving optimal patient care.
Abstract: The gluten-free diet (GFD) has become one of the most popular diets in modern history Claims of improved health and increased energy fuel this popularity, though there is little evidence to substantiate these claims The present review focuses on outlining known gluten-related disorders (GRD), discussing the GFD in the general population, exploring nutritional considerations, and providing advice for physicians in managing these patients Currently, about a quarter of the population reports keeping a GFD despite GRDs affecting less than half of these individuals Reduced intake of calcium, B vitamins, and fiber as well as enhanced consumption of fat and simple carbohydrates has consistently been reported and needs to be continually addressed Although a necessity in proper management of GRDs, unforeseen nutritional complications may develop in patients who are gluten free for which enhanced physician awareness is vital to achieving optimal patient care

Journal ArticleDOI
TL;DR: Higher intake of B vitamins throughout young adulthood was associated with better cognitive function in midlife, and higher intakes of vitamin B-6 resulted in better psychomotor speed measured by DSST scores.

Journal ArticleDOI
TL;DR: Lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults, suggesting that Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing.
Abstract: Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing.

Journal ArticleDOI
TL;DR: The results suggest that one-carbon metabolism plays a significant role in recovery after stroke and MTHFR deficiency contributes to poor recovery from stroke.

Journal ArticleDOI
TL;DR: It is demonstrated that essential 1‐carbon metabolism‐associated micronutrients (1‐CMAMs; i.e., methionine and B vitamins) early in life are crucial in programming later cognition by ES, and nutrition is important in brain programming by ES.
Abstract: Early-life stress (ES) impairs cognition later in life. Because ES prevention is problematic, intervention is needed, yet the mechanisms that underlie ES remain largely unknown. So far, the role of early nutrition in brain programming has been largely ignored. Here, we demonstrate that essential 1-carbon metabolism-associated micronutrients (1-CMAMs; i.e., methionine and B vitamins) early in life are crucial in programming later cognition by ES. ES was induced in male C57Bl/6 mice from postnatal d (P)2-9. 1-CMAM levels were measured centrally and peripherally by using liquid chromatography-mass spectroscopy. Next, we supplemented the maternal diet with 1-CMAM only during the ES period and studied cognitive, neuroendocrine, neurogenic, transcriptional, and epigenetic changes in adult offspring. We demonstrate that ES specifically reduces methionine in offspring plasma and brain. Of note, dietary 1-CMAM enrichment during P2-9 restored methionine levels and rescued ES-induced adult cognitive impairments. Beneficial effects of this early dietary enrichment were associated with prevention of the ES-induced rise in corticosterone and adrenal gland hypertrophy did not involve changes in maternal care, hippocampal volume, neurogenesis, or global/Nr3c1-specific DNA methylation. In summary, nutrition is important in brain programming by ES. A short, early supplementation with essential micronutrients can already prevent lasting effects of ES. This concept opens new avenues for nutritional intervention.-Naninck, E. F. G., Oosterink, J. E., Yam, K.-Y., de Vries, L. P., Schierbeek, H., van Goudoever, J. B., Verkaik-Schakel, R.-N., Plantinga, J. A., Plosch, T., Lucassen, P. J., Korosi, A. Early micronutrient supplementation protects against early stress-induced cognitive impairments.

Journal ArticleDOI
TL;DR: The efficacy and safety of supplementation with vitamins to prevent MCI and the early stages of AD will most likely depend on which pathways are defective, which vitamins are deficient and could correct the relevant metabolic defects, and the modulating impact of nutrient-nutrient and nutrient-genotype interaction.