Showing papers on "B vitamins published in 2018"

Homocysteine and Dementia: An International Consensus Statement.

Abstract: Identification of modifiable risk factors provides a crucial approach to the prevention of dementia. Nutritional or nutrient-dependent risk factors are especially important because dietary modifications or use of dietary supplements may lower the risk factor level. One such risk factor is a raised concentration of the biomarker plasma total homocysteine, which reflects the functional status of three B vitamins (folate, vitamins B12, B6). A group of experts reviewed literature evidence from the last 20 years. We here present a Consensus Statement, based on the Bradford Hill criteria, and conclude that elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer's disease in older persons. In a variety of clinical studies, the relative risk of dementia in elderly people for moderately raised homocysteine (within the normal range) ranges from 1.15 to 2.5, and the Population Attributable risk ranges from 4.3 to 31%. Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline. The findings are consistent with moderately raised plasma total homocysteine (>11 μmol/L), which is common in the elderly, being one of the causes of age-related cognitive decline and dementia. Thus, the public health significance of raised tHcy in the elderly should not be underestimated, since it is easy, inexpensive, and safe to treat with B vitamins. Further trials are needed to see whether B vitamin treatment will slow, or prevent, conversion to dementia in people at risk of cognitive decline or dementia.

Structure of the human activated spliceosome in three conformational states.

Abstract: During each cycle of pre-mRNA splicing, the pre-catalytic spliceosome (B complex) is converted into the activated spliceosome (Bact complex), which has a well-formed active site but cannot proceed to the branching reaction. Here, we present the cryo-EM structure of the human Bact complex in three distinct conformational states. The EM map allows atomic modeling of nearly all protein components of the U2 small nuclear ribonucleoprotein (snRNP), including three of the SF3a complex and seven of the SF3b complex. The structure of the human Bact complex contains 52 proteins, U2, U5, and U6 small nuclear RNA (snRNA), and a pre-mRNA. Three distinct conformations have been captured, representing the early, mature, and late states of the human Bact complex. These complexes differ in the orientation of the Switch loop of Prp8, the splicing factors RNF113A and NY-CO-10, and most components of the NineTeen complex (NTC) and the NTC-related complex. Analysis of these three complexes and comparison with the B and C complexes reveal an ordered flux of components in the B-to-Bact and the Bact-to-B* transitions, which ultimately prime the active site for the branching reaction.

Diet, nutrition and the ageing brain: current evidence and new directions.

Abstract: Globally populations are ageing. By 2050, it is estimated that there will be two billion people aged 60 years or over, of which 131 million are projected to be affected by dementia, while depression is predicted to be the second leading cause of disability worldwide by 2020. Preventing or delaying the onset of these disorders should therefore be a public health priority. There is some evidence linking certain dietary patterns, particularly the Mediterranean diet, with a reduced risk of dementia and depression. Specific dietary components have also been investigated in relation to brain health, with emerging evidence supporting protective roles for n-3 PUFA, polyphenols, vitamin D and B-vitamins. At this time, the totality of evidence is strongest in support of a role for folate and the metabolically related B-vitamins (vitamin B12, vitamin B6 and riboflavin) in slowing the progression of cognitive decline and possibly reducing the risk of depression in ageing. Future studies incorporating new technologies, such as MRI and magnetoencephalography, offer much promise in identifying effective nutrition interventions that could reduce the risk of cognitive and mental disorders. This review will explore the ageing brain and the emerging evidence linking diet and specific nutrients with cognitive function and depression in ageing, with the potential to develop strategies that could improve quality of life in our ageing population.

The Drosophila melanogaster Gut Microbiota Provisions Thiamine to Its Host

Abstract: The microbiota of Drosophila melanogaster has a substantial impact on host physiology and nutrition. Some effects may involve vitamin provisioning, but the relationships between microbe-derived vitamins, diet, and host health remain to be established systematically. We explored the contribution of microbiota in supplying sufficient dietary thiamine (vitamin B1) to support D. melanogaster at different stages of its life cycle. Using chemically defined diets with different levels of available thiamine, we found that the interaction of thiamine concentration and microbiota did not affect the longevity of adult D. melanogaster. Likewise, this interplay did not have an impact on egg production. However, we determined that thiamine availability has a large impact on offspring development, as axenic offspring were unable to develop on a thiamine-free diet. Offspring survived on the diet only when the microbiota was present or added back, demonstrating that the microbiota was able to provide enough thiamine to support host development. Through gnotobiotic studies, we determined that Acetobacter pomorum, a common member of the microbiota, was able to rescue development of larvae raised on the no-thiamine diet. Further, it was the only microbiota member that produced measurable amounts of thiamine when grown on the thiamine-free fly medium. Its close relative Acetobacter pasteurianus also rescued larvae; however, a thiamine auxotrophic mutant strain was unable to support larval growth and development. The results demonstrate that the D. melanogaster microbiota functions to provision thiamine to its host in a low-thiamine environment. IMPORTANCE There has been a long-standing assumption that the microbiota of animals provides their hosts with essential B vitamins; however, there is not a wealth of empirical evidence supporting this idea, especially for vitamin B1 (thiamine). To determine whether this assumption is true, we used Drosophila melanogaster and chemically defined diets with different thiamine concentrations as a model. We found that the microbiota does provide thiamine to its host, enough to allow the development of flies on a thiamine-free diet. The power of the Drosophila-microbiota system allowed us to determine that one microbiota member in particular, Acetobacter pomorum, is responsible for the thiamine provisioning. Thereby, our study verifies this long-standing hypothesis. Finally, the methods used in this work are applicable for interrogating the underpinnings of other aspects of the tripartite interaction between diet, host, and microbiota.

Menstrual Cycle Rhythmicity: Metabolic Patterns in Healthy Women

Abstract: The menstrual cycle is an essential life rhythm governed by interacting levels of progesterone, estradiol, follicular stimulating, and luteinizing hormones. To study metabolic changes, biofluids were collected at four timepoints in the menstrual cycle from 34 healthy, premenopausal women. Serum hormones, urinary luteinizing hormone and self-reported menstrual cycle timing were used for a 5-phase cycle classification. Plasma and urine were analyzed using LC-MS and GC-MS for metabolomics and lipidomics; serum for clinical chemistries; and plasma for B vitamins using HPLC-FLD. Of 397 metabolites and micronutrients tested, 208 were significantly (p < 0.05) changed and 71 reached the FDR 0.20 threshold showing rhythmicity in neurotransmitter precursors, glutathione metabolism, the urea cycle, 4-pyridoxic acid, and 25-OH vitamin D. In total, 39 amino acids and derivatives and 18 lipid species decreased (FDR < 0.20) in the luteal phase, possibly indicative of an anabolic state during the progesterone peak and recovery during menstruation and the follicular phase. The reduced metabolite levels observed may represent a time of vulnerability to hormone related health issues such as PMS and PMDD, in the setting of a healthy, rhythmic state. These results provide a foundation for further research on cyclic differences in nutrient-related metabolites and may form the basis of novel nutrition strategies for women.

Hyperhomocysteinemia as a Risk Factor for Vascular Contributions to Cognitive Impairment and Dementia.

Abstract: Behind only Alzheimer's disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10-40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, preclinical and clinical data shows it is not. Clinical trials using B vitamin supplementation have shown conflicting results about the benefits of lowering homocysteine and issues have arisen over proper study design within the trials. Studies using cell culture and animal models have proposed several mechanisms for homocysteine-induced cognitive decline, providing other targets for therapeutics. For this review, we will focus on HHcy as a risk factor for VCID, specifically, the different mechanisms proposed for homocysteine-induced cognitive decline and the clinical trials aimed at lowering plasma homocysteine.

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change: a randomised trial

Abstract: Low fruit and vegetable consumption is linked with an increased risk of death from vascular disease and cancer The benefit of eating fruits and vegetables is attributed in part to antioxidants, vitamins and phytochemicals Whether increasing intake impacts on markers of disease remains to be established This study investigates whether increasing daily intake of fruits, vegetables and juices from low (approx 3 portions), to high intakes (approx 8 portions) impacts on nutritional and clinical biomarkers Barriers to achieving the recommended fruit and vegetable intakes are also investigated In a randomised clinical trial, the participants [19 men and 26 women (39–58 years)] with low reported fruit, juice and vegetable intake (<3 portions/day) were randomised to consume either their usual diet or a diet supplemented with an additional 480 g of fruit and vegetables and fruit juice (300 ml) daily for 12 weeks Nutritional biomarkers (vitamin C, carotenoids, B vitamins), antioxidant capacity and genomic stability were measured pre-intervention, at 4-, 8- and 12 weeks throughout the intervention Samples were also taken post-intervention after a 6-week washout period Glucose, homocysteine, lipids, blood pressure, weight and arterial stiffness were also measured Intake of fruit, fruit juice and vegetables was reassessed 12 months after conducting the study and a questionnaire was developed to identify barriers to healthy eating Intake increased significantly in the intervention group compared to controls, achieving 84 portions/day after 12 weeks Plasma vitamin C (35%), folate (15%) and certain carotenoids [α-carotene (50%) and β-carotene (70%) and lutein/zeaxanthin (70%)] were significantly increased (P < 005) in the intervention group There were no significant changes in antioxidant capacity, DNA damage and markers of vascular health Barriers to achieving recommended intakes of fruits and vegetables measured 12 months after the intervention period were amount, inconvenience and cost While increasing fruit, juice and vegetable consumption increases circulating level of beneficial nutrients in healthy subjects, a 12-week intervention was not associated with effects on antioxidant status or lymphocyte DNA damage This trial was registered at Controlled-Trialscom; registration ISRCTN71368072

Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation

Abstract: The precatalytic spliceosome (B complex) is preceded by the pre-B complex. Here we report the cryo–electron microscopy structures of the Saccharomyces cerevisiae pre-B and B complexes at average resolutions of 3.3 to 4.6 and 3.9 angstroms, respectively. In the pre-B complex, the duplex between the 5′ splice site (5′SS) and U1 small nuclear RNA (snRNA) is recognized by Yhc1, Luc7, and the Sm ring. In the B complex, U1 small nuclear ribonucleoprotein is dissociated, the 5′-exon–5′SS sequences are translocated near U6 snRNA, and three B-specific proteins may orient the precursor messenger RNA. In both complexes, U6 snRNA is anchored to loop I of U5 snRNA, and the duplex between the branch point sequence and U2 snRNA is recognized by the SF3b complex. Structural analysis reveals the mechanism of assembly and activation for the yeast spliceosome.

Breakfast in the United States: Food and Nutrient Intakes in Relation to Diet Quality in National Health and Examination Survey 2011⁻2014. A Study from the International Breakfast Research Initiative.

Abstract: The contribution of breakfast to diet quality (DQ) can inform future dietary guidelines This study examined breakfast nutrition in relation to overall DQ, using dietary data from the first reported day of the National Health and Examination Survey (NHANES) 2011–2014 (n = 14,488) Relative DQ was assessed using the Nutrient Rich Foods Index (NRF93) and the USDA Healthy Eating Index 2015 (HEI 2015) The sample was stratified by NRF93 tertiles and by age and socioeconomic groups Four out of 5 NHANES participants had breakfast on the day of the interview Breakfast provided 19–22% of dietary energy depending on age Breakfast intakes of complex carbohydrates and total sugars were proportionately higher and intakes of protein and fats were lower relative to breakfast energy intakes Breakfast provided more that 20% of daily intakes of B vitamins, vitamins A and D, folate, calcium, iron, potassium and magnesium Eating breakfast was associated with higher NRF93 DQ scores Breakfasts associated with the top tertile of NRF93 scores had less added sugars and fats than those associated with the bottom tertile Such breakfasts had more fruit and juices, more whole grain products, more milk and yogurt and less meat and eggs Breakfast patterns and food choices that favored fruit, whole grains and dairy were associated with healthiest diets

Structures of the human pre-catalytic spliceosome and its precursor spliceosome.

Abstract: The pre-catalytic spliceosome (B complex) is preceded by its precursor spliceosome (pre-B complex) and followed by the activated spliceosome (Bact complex). The pre-B-to-B and B-to-Bact transitions are driven by the ATPase/helicases Prp28 and Brr2, respectively. In this study, we report the cryo-electron microscopy structures of the human pre-B complex and the human B complex at an average resolution of 5.7 and 3.8 A, respectively. In the pre-B complex, U1 and U2 small nuclear ribonucleoproteins (snRNPs) associate with two edges of the tetrahedron-shaped U4/U6.U5 tri-snRNP. The pre-mRNA is yet to be recognized by U5 or U6 small nuclear RNA (snRNA), and loop I of U5 snRNA remains unengaged. In the B complex, U1 snRNP and Prp28 are dissociated, the 5’-exon is anchored to loop I of U5 snRNA, and the 5′-splice site is recognized by U6 snRNA through duplex formation. In sharp contrast to S. cerevisiae, most components of U2 snRNP and tri-snRNP, exemplified by Brr2, undergo pronounced rearrangements in the human pre-B-to-B transition. Structural analysis reveals mechanistic insights into the assembly and activation of the human spliceosome.

The Effect of Kyolic Aged Garlic Extract on Gut Microbiota, Inflammation, and Cardiovascular Markers in Hypertensives: The GarGIC Trial.

Abstract: Background: Previous research suggests Kyolic-aged-garlic-extract to be effective in reducing blood pressure in a large proportion of hypertensive patients similar to first-line standard antihypertensive medication. High blood pressure has been linked to gut dysbiosis, with a significant decrease in microbial richness and diversity in hypertensives compared to normotensives. Furthermore, gut dysbiosis has been associated with increased inflammatory status and risk of cardiovascular events. Objective: To assess the effect of Kyolic aged GARlic extract on Gut microbiota, Inflammation, and Cardiovascular markers, including blood pressure, pulse wave velocity and arterial stiffness. Methods: A total of 49 participants with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12-weeks, investigating the effect of daily intake of aged-garlic-extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, pulse wave velocity and arterial stiffness, inflammatory markers, and gut microbiota. Results: Mean blood pressure was significantly reduced by 10 ± 3.6 mmHg systolic and 5.4 ± 2.3 mmHg diastolic compared to placebo. Vitamin B12 status played a role in responsiveness to garlic on blood pressure in 17% of patients. Garlic significantly lowered central blood pressure, pulse pressure and arterial stiffness (p < 0.05). Trends observed in inflammatory markers TNF-α and IL-6 need to be confirmed in larger trials. Furthermore, aged-garlic-extract improved gut microbiota, evident by higher microbial richness and diversity with a marked increase in Lactobacillus and Clostridia species after 3 months of supplementation. Conclusions: Kyolic-aged-garlic-extract is effective in reducing blood pressure in patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and gut microbial profile. Aged-garlic-extract is highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment, with multiple benefits for cardiovascular health. Trial Registration: Australian New Zealand Clinical Trial Registry ACTRN12616000185460 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370096).

The Effect of a High-Dose Vitamin B Multivitamin Supplement on the Relationship between Brain Metabolism and Blood Biomarkers of Oxidative Stress: A Randomized Control Trial

Abstract: A diet rich in B-group vitamins is essential for optimal body and brain function, and insufficient amounts of such vitamins have been associated with higher levels of neural inflammation and oxidative stress, as marked by increased blood plasma homocysteine. Neural biomarkers of oxidative stress quantified through proton magnetic spectroscopy (1H-MRS) are not well understood, and the relationship between such neural and blood biomarkers is seldom studied. The current study addresses this gap by investigating the direct effect of 6-month high-dose B-group vitamin supplementation on neural and blood biomarkers of metabolism. Using a randomized, double-blind, placebo-controlled design, 32 healthy adults (20 female, 12 male) aged 30–65 years underwent blood tests (vitamin B6, vitamin B12, folate, and homocysteine levels) and 1H-MRS of the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) before and after supplementation. Results confirmed the supplement was effective in increasing vitamin B6 and vitamin B12 levels and reducing homocysteine, whereas there was no change in folate levels. There were significant relationships between vitamin B6 and N-acetylaspartate (NAA), choline, and creatine, as well as between vitamin B12 and creatine (ps 0.05). Together these data provide preliminary evidence for the efficacy of high-dose B-group supplementation in reducing oxidative stress and inflammation through increasing oxidative metabolism. It may also promote myelination, cellular metabolism, and energy storage.

Effect of dietary interventions in mild cognitive impairment: a systematic review.

Abstract: Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed, particularly in a mild cognitive impairment (MCI) population. This review examined the effect of diet on cognitive outcomes in MCI patients. A total of five databases were searched to find randomised controlled trial (RCT) studies, with diet as the main focus, in MCI participants. The primary outcome was incident dementia and/or Alzheimer's disease (AD) and secondary outcomes included cognitive function across different domains using validated neuropsychological tests. Sixteen studies met the inclusion criteria. There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making study comparisons difficult. Supplementation with vitamin E (one study, n 516), ginkgo biloba (one study, n 482) or Fortasyn Connect (one study, n 311) had no significant effect on progression from MCI to dementia and/or AD. For cognitive function, the findings showed some improvements in performance, particularly in memory, with the most consistent results shown by B vitamins, including folic acid (one study, n 266), folic acid alone (one study, n 180), DHA and EPA (two studies, n 36 and n 86), DHA (one study, n 240) and flavonol supplementation (one study, n 90). The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients. Further well-designed trials are needed, with standardised and robust measures of cognition to investigate the influence of diet on cognitive status.

The Levels of Vitamin D, Vitamin D Receptor, Homocysteine and Complex B Vitamin in Children with Autism Spectrum Disorders

Abstract: Objective Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome with an increasingly prevalent etiology, yet not fully understood. It has been thought that vitamin D, complex B vitamin levels and homocysteine are associated with environmental factors and are important in ASD. The aim of this study was to examine serum vitamin D, vitamin D receptor (VDR), homocysteine, vitamin B6, vitamin B12 and folate levels in ASD. Methods In this study, serum vitamin D and VDR, homocysteine, vitamins B6, B12 and folate levels were determined in 60 patients with ASD (aged 3 to 12 years) and in 45 age-gender matched healthy controls. In addition, calcium, phosphorus and alkaline phosphatase, which are associated with vitamin D metabolism, were measured from serum in both groups. ASD severity was evaluted by the Childhood Autism Rating Scale (CARS). Results Serum vitamin D and VDR were substantially reduced in patients with ASD in comparision to control group. However, homocysteine level was significantly higher and vitamin B6, vitamin B12 and folate were also reduced in patients with ASD. Total CARS score showed a positive association with homocysteine and a negative correlation with vitamins D,B6, B12, folate and VDR. Conclusion This comprehensive study, which examines many parameters has shown that low serum levels of vitamins D, B6, B12, folate and VDR as well as high homocysteine are important in the etiopathogenesis of ASD. However, further studies are required to define the precise mechanism(s) of these parameters and their contributions to the etiology and treatment of ASD.

Configuration of ten light-harvesting chlorophyll a/b complex I subunits in Chlamydomonas reinhardtii photosystem I.

Abstract: In plants, the photosystem I (PSI) core complex stably associates with its light-harvesting chlorophyll a/b complex I (LHCI) to form the PSI-LHCI supercomplex. The vascular plant PSI core complex associates with four distinct LHCI subunits, whereas that of the green alga Chlamydomonas reinhardtii binds nine distinct LHCI subunits (LHCA1–LHCA9). The stoichiometry and configuration of these LHCI subunits in the PSI-LHCI supercomplex of C. reinhardtii remain controversial. Here, we determined the stoichiometry of the nine distinct LHCI subunits relative to PSI subunits through uniform labeling of total proteins using 14C. We separated the nine LHCI polypeptides by three different sodium dodecyl sulfate-polyacrylamide gel electrophoresis systems. Our data revealed that the PSI-LHCI supercomplex contains two LHCA1 proteins and one of each of the other eight LHCI subunits. Subsequently, we identified their cross-linked products by immunodetection and mass spectrometry to determine the configuration of the 10 LHCI subunits within the PSI-LHCI supercomplex. Furthermore, analyses of PSI-LHCI complexes isolated from ΔLHCA2 and ΔLHCA5 mutants and oligomeric LHCI from a PSI-deficient (ΔpsaA/B) mutant provided supporting evidence for the LHCI subunit configuration. In conclusion, eight LHCI subunits bind to the PSI core at the site of PSAF subunit in two layers: LHCA1-LHCA8-LHCA7-LHCA3 from PSAG to PSAK, in the inner layer, and LHCA1-LHCA4-LHCA6-LHCA5 in the outer layer. The other two LHCI subunits, LHCA2 and LHCA9, bind PSAB between PSAG and PSAH, PSAG-LHCA9-LHCA2-PSAH. Our study provides new insights into the LHCI configuration linked to the PSI core.

Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3)

Abstract: Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospecti ...

Breakfast Consumption in the UK: Patterns, Nutrient Intake and Diet Quality. A Study from the International Breakfast Research Initiative Group

Abstract: Breakfast consumption is associated with higher overall dietary adequacy; however, there is a lack of quantitative guidelines for optimal nutrient intakes at breakfast in the UK. This study aimed to investigate nutrient and food group intakes at breakfast and examine their relationship to overall Diet Quality (DQ). Data from the most recent National Diet and Nutrition Survey (NDNS, 2008–2014) were accessed to provide a representative sample (n = 8174) of the UK population, aged 5–96 years, mean age of 33 years. Food intake was measured by a 4-day estimated food diary and DQ was assessed by the Nutrient Rich Food Index 9.3 method. Energy- and socio-economic-adjusted nutrient and food group intakes were compared across age groups and DQ tertiles by ANCOVA. Breakfast contributed 20–22% to total energy intake. Breakfast intakes of carbohydrate and non-milk extrinsic sugars (NMES) were higher, and intakes of protein, total fat and saturated fatty acid (SFA) were lower, than relative daily intakes. Breakfast was particularly rich in B vitamins, vitamin D, calcium, iron, iodine and magnesium. From the lowest to the highest DQ tertile decreasing intakes of NMES, SFA and total fat and increasing intakes of carbohydrate, protein, fibre and most micronutrients were found. These findings could help to inform the development of nutrient-based recommendations for a balanced breakfast for the first time in the UK.

Mosaic patterns of B-vitamin synthesis and utilization in a natural marine microbial community.

Abstract: Aquatic environments contain large communities of microorganisms whose synergistic interactions mediate the cycling of major and trace nutrients, including vitamins. B-vitamins are essential coenzymes that many organisms cannot synthesize. Thus, their exchange among de novo synthesizers and auxotrophs is expected to play an important role in the microbial consortia and explain some of the temporal and spatial changes observed in diversity. In this study, we analyzed metatranscriptomes of a natural marine microbial community, diel sampled quarterly over one year to try to identify the potential major B-vitamin synthesizers and consumers. Transcriptomic data showed that the best-represented taxa dominated the expression of synthesis genes for some B-vitamins but lacked transcripts for others. For instance, Rhodobacterales dominated the expression of vitamin-B12 synthesis, but not of vitamin-B7 , whose synthesis transcripts were mainly represented by Flavobacteria. In contrast, bacterial groups that constituted less than 4% of the community (e.g., Verrucomicrobia) accounted for most of the vitamin-B1 synthesis transcripts. Furthermore, ambient vitamin-B1 concentrations were higher in samples collected during the day, and were positively correlated with chlorophyll-a concentrations. Our analysis supports the hypothesis that the mosaic of metabolic interdependencies through B-vitamin synthesis and exchange are key processes that contribute to shaping microbial communities in nature.

Multiple Acquisitions of Pathogen-Derived Francisella Endosymbionts in Soft Ticks

Abstract: Bacterial endosymbionts of ticks are of interest due to their close evolutionary relationships with tick-vectored pathogens. For instance, whereas many ticks contain Francisella-like endosymbionts (FLEs), others transmit the mammalian pathogen Francisella tularensis. We recently sequenced the genome of an FLE present in the hard tick Amblyomma maculatum (FLE-Am) and showed that it likely evolved from a pathogenic ancestor. In order to expand our understanding of FLEs, in the current study we sequenced the genome of an FLE in the soft tick Ornithodoros moubata and compared it to the genomes of FLE-Am, Francisella persica-an FLE in the soft tick Argus (Persicargas) arboreus, Francisella sp. MA067296-a clinical isolate responsible for an opportunistic human infection, and F. tularensis, the established human pathogen. We determined that FLEs and MA067296 belonged to a sister taxon of mammalian pathogens, and contained inactivated versions of virulence genes present in F. tularensis, indicating that the most recent common ancestor shared by FLEs and F. tularensis was a potential mammalian pathogen. Our analyses also revealed that the two soft ticks (O. moubata and A. arboreus) probably acquired their FLEs separately, suggesting that the virulence attenuation observed in FLEs are not the consequence of a single acquisition event followed by speciation, but probably due to independent transitions of pathogenic francisellae into nonpathogenic FLEs within separate tick lineages. Additionally, we show that FLEs encode intact pathways for the production of several B vitamins and cofactors, denoting that they could function as nutrient-provisioning endosymbionts in ticks.

To B or Not to B: Comparative Genomics Suggests Arsenophonus as a Source of B Vitamins in Whiteflies.

Abstract: Insect lineages feeding on nutritionally restricted diets such as phloem sap, xylem sap, or blood, were able to diversify by acquiring bacterial species that complement lacking nutrients. These bacteria, considered obligate/primary endosymbionts, share a long evolutionary history with their hosts. In some cases, however, these endosymbionts are not able to fulfill all of their host's nutritional requirements, driving the acquisition of additional symbiotic species. Phloem-feeding members of the insect family Aleyrodidae (whiteflies) established an obligate relationship with Candidatus Portiera aleyrodidarum, which provides its hots with essential amino acids and carotenoids. In addition, many whitefly species harbor additional endosymbionts which may potentially further supplement their host's diet. To test this hypothesis, genomes of several endosymbionts of the whiteflies Aleurodicus dispersus, Aleurodicus floccissimus and Trialeurodes vaporariorum were analyzed. In addition to Portiera, all three species were found to harbor one Arsenophonus and one Wolbachia endosymbiont. A comparative analysis of Arsenophonus genomes revealed that although all three are capable of synthesizing B vitamins and cofactors, such as pyridoxal, riboflavin, or folate, their genomes and phylogenetic relationship vary greatly. Arsenophonus of A. floccissimus and T. vaporariorum belong to the same clade, and display characteristics of facultative endosymbionts, such as large genomes (3 Mb) with thousands of genes and pseudogenes, intermediate GC content, and mobile genetic elements. In contrast, Arsenophonus of A. dispersus belongs to a different lineage and displays the characteristics of a primary endosymbiont-a reduced genome (670 kb) with ~400 genes, 32% GC content, and no mobile genetic elements. However, the presence of 274 pseudogenes suggests that this symbiotic association is more recent than other reported primary endosymbionts of hemipterans. The gene repertoire of Arsenophonus of A. dispersus is completely integrated in the symbiotic consortia, and the biosynthesis of most vitamins occurs in shared pathways with its host. In addition, Wolbachia endosymbionts have also retained the ability to produce riboflavin, flavin adenine dinucleotide, and folate, and may make a nutritional contribution. Taken together, our results show that Arsenophonus hold a pivotal place in whitefly nutrition by their ability to produce B vitamins.

Toward Eradication of B-Vitamin Deficiencies: Considerations for Crop Biofortification.

Abstract: 'Hidden hunger' involves insufficient intake of micronutrients and is estimated to affect over two billion people on a global scale. Malnutrition of vitamins and minerals is known to cause an alarming number of casualties, even in the developed world. Many staple crops, although serving as the main dietary component for large population groups, deliver inadequate amounts of micronutrients. Biofortification, the augmentation of natural micronutrient levels in crop products through breeding or genetic engineering, is a pivotal tool in the fight against micronutrient malnutrition (MNM). Although these approaches have shown to be successful in several species, a more extensive knowledge of plant metabolism and function of these micronutrients is required to refine and improve biofortification strategies. This review focuses on the relevant B-vitamins (B1, B6, and B9). First, the role of these vitamins in plant physiology is elaborated, as well their biosynthesis. Second, the rationale behind vitamin biofortification is illustrated in view of pathophysiology and epidemiology of the deficiency. Furthermore, advances in biofortification, via metabolic engineering or breeding, are presented. Finally, considerations on B-vitamin multi-biofortified crops are raised, comprising the possible interplay of these vitamins in planta.

Efficacy of a Therapeutic Diet on Dogs With Signs of Cognitive Dysfunction Syndrome (CDS): A Prospective Double Blinded Placebo Controlled Clinical Study.

Abstract: Cognitive dysfunction syndrome (CDS) is a common condition in senior dogs, which may be analogous to dementia such as Alzheimer's disease (AD) in people. In humans, AD has been associated with many risk factors such as reduced cerebral glucose metabolism, docosahexaenoic acid (DHA) deficiency, chronic oxidative stress, and chronic inflammation. By targeting some of these risk factors, we have developed two nutritional solutions (medium chain triglyceride, MCT and Brain Protection Blend, BPB) to enhance cognitive function and slow aging-induced cognitive decline. These have been positively evaluated in colony housed senior dogs and cats. The objective of this clinical study was to evaluate the effects of diets with MCTs and the BPB on client-owned dogs with CDS. Participating veterinary clinics screened senior dogs for signs of CDS as determined by a Senior Canine Behavior Questionnaire and a Canine Medical Health Questionnaire. Eighty-seven dogs were randomly enrolled into one of three diet groups with 29 dogs per group: Control, 6.5% MCT oil + BPB (6.5% MCT diet), 9% MCT oil + BPB (9% MCT diet). Diets were fed for a period of 90 days, and each dog's CDS signs were re-evaluated at day 30 and day 90. All 6 categories of the CDS signs were significantly improved (p <0.05) in the dogs given the 6.5% MCT diet at the end of the 90-day study. Control only improved in 4 out 6 categories. The 9% MCT diet only improved in dogs that accepted the diet. The results from this dog study confirm the benefits of MCT and BPB in managing clinical signs of CDS in dogs. The results support our hypothesis that targeting known risk factors associated with brain aging and AD is able to improve symptoms of CDS in dogs. These data may facilitate the development of similar nutrient blends to manage MCI and AD.

Voluntary fortification is ineffective to maintain the vitamin B12 and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA).

Abstract: Mandatory fortification of staple grains with folic acid and/or vitamin B12 (B12) is under debate in many countries including Ireland, which has a liberal, but voluntary, fortification policy. Older adults can be at risk of both deficiency and high folate status, although little is known on the actual prevalence and the major predictors. Population prevalence estimates from older adults (n 5290 ≥50 years) from the Irish Longitudinal Study on Ageing (TILDA) (Wave 1) are presented here. Measures included plasma total vitamin B12 and folate, whereas predictors included detailed demographic, socio-economic, geographic, seasonal and health/lifestyle data. The prevalence of deficient or low B12 status (45 nmol/l) was observed in 8·9 %, whereas high B12 status was observed in 3·1 % (>601 pmol/l). The largest positive predictor of B12 concentration was self-reported B12 injection and/or supplement use (coefficient 51·5 pmol/; 95 % CI 9·4, 93·6; P=0·016) followed by sex and geographic location. The largest negative predictor was metformin use (-33·6; 95 % CI -51·9, -15·4; P<0·0001). The largest positive predictor of folate concentration was folic acid supplement use (6·0; 95 % CI 3·0, 9·0 nmol/l; P<0·001) followed by being female and statin medications. The largest negative predictor was geographic location (-5·7; 95 % CI -6·7, -4·6; P<0·0001) followed by seasonality and smoking. B-vitamin status in older adults is affected by health and lifestyle, medication, sampling period and geographic location. We observed a high prevalence of low B12 and folate status, indicating that the current policy of voluntary fortification is ineffective for older adults.

Robust interaction of IFT70 with IFT52–IFT88 in the IFT-B complex is required for ciliogenesis

Abstract: In the intraflagellar transport (IFT) machinery, the IFT-B and IFT-A complexes mediate anterograde and retrograde ciliary protein trafficking, respectively. Among the 16 subunits of the IFT-B complex, several subunits are essential for ciliogenesis, whereas others, which are associated peripherally with the complex, are dispensable for ciliogenesis but play a role in protein trafficking. IFT22-knockout (KO) cells established in this study demonstrated no defects in ciliogenesis or ciliary protein trafficking. In stark contrast, IFT70A and IFT70B double-knockout cells did not form cilia, even though IFT70 is associated peripherally with the IFT-B complex via the IFT52-IFT88 dimer, and other IFT-B subunits assembled at the ciliary base in the absence of IFT70. Exogenous expression of either IFT70A or IFT70B restored the ciliogenesis defect of IFT70-KO cells, indicating their redundant roles. IFT70 has 15 consecutive tetratricopeptide repeats (TPRs) followed by a short helix (α36). Deletion of the first TPR or α36 of IFT70A greatly reduced its ability to interact with the IFT52-IFT88 dimer. Exogenous expression of any of the IFT70A deletion mutants in IFT70-KO cells could not restore ciliogenesis. These results show that IFT70 plays an essential role in ciliogenesis, although it is dispensable for assembly of the residual IFT-B subunits.

B vitamins for stroke prevention

Abstract: Supplementation with B vitamins (vitamin B9(folic acid), vitamin B12 and vitamin B6) lowers blood total homocysteine (tHcy) concentrations by about 25% and reduces the relative risk of stroke overall by about 10% (risk ratio (RR) 0.90, 95% CI 0.82 to 0.99) compared with placebo. Homocysteine-lowering interventions have no significant effect on myocardial infarction, death from any cause or adverse outcomes. Factors that appear to modify the effect of B vitamins on stroke risk include low folic acid status, high tHcy, high cyanocobalamin dose in patients with impaired renal function and concurrent antiplatelet therapy. In regions with increasing levels or established policies of population folate supplementation, evidence from observational genetic epidemiological studies and randomised controlled clinical trials is concordant in suggesting an absence of benefit from lowering of homocysteine with folic acid for prevention of stroke. Clinical trials indicate that in countries which mandate folic acid fortification of food, folic acid supplementation has no significant effect on reducing stroke risk (RR 1.05, 95% CI 0.90 to 1.23). However, in countries without mandatory folic acid food fortification, folic acid supplementation reduces the risk of stroke by about 15% (RR 0.85, 95% CI 0.77 to 0.94). Folic acid alone or in combination with minimal cyanocobalamin (≤0.05 mg/day) is associated with an even greater reduction in risk of future stroke by 25% (RR 0.75, 95% CI 0.66 to 0.86), whereas the combination of folic acid and a higher dose of cyanocobalamin (≥0.4 mg/day) is not associated with a reduced risk of future stroke (RR 0.95, 95% CI 0.86 to 1.05). The lack of benefit of folic acid plus higher doses of cyanocobalamin (≥0.4 mg/day) was observed in trials which all included participants with chronic kidney disease. Because metabolic B12 deficiency is very common and usually not diagnosed, future randomised trials of homocysteine-lowering interventions for stroke prevention should probably test a combination of folic acid and methylcobalamin or hydroxocobalamin instead of cyanocobalamin, and perhaps vitamin B6.

Cardioembolic stroke: everything has changed

Abstract: Historically, because of the difficulty of using warfarin safely and effectively, many patients with cardioembolic stroke who should have been anticoagulated were instead given ineffective antiplatelet therapy (or no antithrombotic therapy). With the arrival of new oral anticoagulants that are not significantly more likely than aspirin to cause severe haemorrhage, everything has changed. Because antiplatelet agents are much less effective in preventing cardioembolic stroke, it is now more prudent to anticoagulate patients in whom cardioembolic stroke is strongly suspected. Recent advances include the recognition that intermittent atrial fibrillation is better detected with more prolonged monitoring of the cardiac rhythm, and that percutaneous closure of patent foramen ovale (PFO) may reduce the risk of stroke. However, because in most patients with stroke and PFO the PFO is incidental, this should be reserved for patients in whom paradoxical embolism is likely. A high shunt grade on transcranial Doppler saline studies, and clinical clues to paradoxical embolism, can help in appropriate selection of patients for percutaneous closure. For patients with atrial fibrillation who cannot be anticoagulated, ablation of the left atrial appendage is an emerging option. It is also increasingly recognised that high levels of homocysteine, often due to undiagnosed metabolic deficiency of vitamin B12, markedly increase the risk of stroke in atrial fibrillation, and that B vitamins (folic acid and B12) do prevent stroke by lowering homocysteine. However, with regard to B12, methylcobalamin should probably be used instead of cyanocobalamin. Many important considerations for judicious application of therapies to prevent cardioembolic stroke are discussed.