No description available.

Beans are a commonly consumed food and a staple in many regions worldwide. Pinto beans (Phaseolus vulgaris), categorized as legumes, are dried seeds from plants and are high in protein, carbohydrate and fiber, and low in fat. They are also a good source of various minerals and well as thiamin, riboflavin, niacin, vitamin B6, and folate Beans are typically soaked and thermally processed before consumption. Different processing methods can impact the composition of beans. The purpose of this study was to examine the effect of thermal treatments on vitamin concentration in pinto beans. Beans were simmered, canned, dried-flaked, or dried-extruded, and measured for thiamin, riboflavin, folate, and vitamin B6. Beans were then reheated and measured again for vitamin concentration. Vitamin loss was comparable between the most commonly consumed stages of processing: Simmered, canned reheated, dried-flaked reheated and dried-extruded reheated. The only statistically significant differences were that simmering caused the least amount of degradation of thiamin and dried-flaked product had the least amount of vitamin B6 degradation. Though dried-flaked and dried-extruded beans generally decreased in vitamin concentration, these two products were comparable to the simmered and canned reheated products. This suggests that drying is a nutritionally acceptable means of processing pinto beans, resulting in products that are more economical to transport and more convenient to prepare.

Submitted in fulfillment of the requirements of the degree of Doctor of Technology: Health Sciences, Durban University of Technology, Durban, South Africa, 2015. / Background: In a vulnerable low-income group with a confirmed high risk of cardiovascular disease, like the elderly in the Sharpeville care centre, an acute intervention is needed in order to improve their health profile. Previous studies suggested homocysteine lowering by vitamin B12, B6 and folate supplementation. The effect of vitamin B12, B6 and folate supplementation on the inflammatory response, thrombotic risk, lipid profile, hypertension, risk of metabolic syndrome and homocysteine metabolism in an elderly, black South African population has never been reported. Objectives: The main aim of this interventional study was to assess the effect of vitamins B12, B6 and folate supplementation at 200% RDA for six months on cardiovascular risk markers of an elderly semi-urbanised black South African community. Design: This study was an experimental intervention non-equivalent control group study design in 104 purposively selected samples of all the elderly attending the day-care centre. Setting and participants: A homogeneous group of respondents was included in the study. All subjects were equivalent in age (>60 years), race (black), unemployed/pensioners (socio-demographic) and 60 years and older attending a day care centre in Sharpeville, situated in the Vaal region, Gauteng, SA. Measurements: The distinctiveness of this study lies in the broad panel of parameters evaluating the CVR in correlation with the increased nutritional intake of vitamin B6, B12 and folate. These included: weight, height, waist, serum cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, blood pressure, fibrinogen, high-sensitivity C-reactive protein (HS–CRP), homocysteine, vitamin B12, folate, glucose, insulin, adiponectin and fibronectin. Results: A very high incidence (66.36%) of hyperhomocysteinaemia is present in the sample. The mean serum homocysteine level in hyperhomocysteinaemic individuals decreased statistically significantly from 25.00±8.00 umol/l to 18.80±12.00 umol/l after the intervention. The number of respondents with an increased homocysteine level decreased from 100% (baseline) to 67% (follow-up). The supplementation was beneficial (statistically significant changes) to the glucose levels, fibrinolytic status, vitamin B6 serum levels, fibronectin levels and haemopoeiesis (decreased macrocytosis) of all the individuals (regardless of their homocysteine status). Conclusion: It is concluded that supplementation of vitamins B6, B12 and folate at 200% RDA for six months is an effective homocysteine-lowering approach as a strategy to reduce hyperhomocysteinaemia in an elderly population and thereby reduce cardiovascular risk (CVR). The supplementation intervention mentioned is not an effective multifactorial strategy to decrease CVR although beneficial effects were found with other CVR markers independent of homocysteine status.

In this thesis I study a variety of two-dimensional turbulent systems using a mixed analytical, phenomenological and numerical approach. The systems under consideration are governed by the two-dimensional Navier-Stokes (2DNS), surface quasigeostrophic (SQG), alpha-turbulence and magnetohydrodynamic (MHD) equations. The main analytical focus is on the number of degrees of freedom of a given system, defined as the least value $N$ such that all $n$-dimensional ($n$ ≥ $N$) volume elements along a given trajectory contract during the course of evolution. By equating $N$ with the number of active Fourier-space modes, that is the number of modes in the inertial range, and assuming power-law spectra in the inertial range, the scaling of $N$ with the Reynolds number $Re$ allows bounds to be put on the exponent of the spectrum. This allows the recovery of analytic results that have until now only been derived phenomenologically, such as the $k$[superscript(-5/3)] energy spectrum in the energy inertial range in SQG turbulence. Phenomenologically I study the modal interactions that control the transfer of various conserved quantities. Among other results I show that in MHD dynamo triads (those converting kinetic into magnetic energy) are associated with a direct magnetic energy flux while anti-dynamo triads (those converting magnetic into kinetic energy) are associated with an inverse magnetic energy flux. As both dynamo and anti-dynamo interacting triads are integral parts of the direct energy transfer, the anti-dynamo inverse flux partially neutralises the dynamo direct flux, arguably resulting in relatively weak direct energy transfer and giving rise to dynamo saturation. These theoretical results are backed up by high resolution numerical simulations, out of which have emerged some new results such as the suggestion that for alpha turbulence the generalised enstrophy spectra are not closely approximated by those that have been derived phenomenologically, and new theories may be needed in order to explain them.

No description available.

The aim of this study was to investigate the vitamin B-6 status of Saudi adult males and compare the status between rural and urban subjects. Fifty-one adult male subjects were recruited from urban (n=31) and rural (n=20) populations of Riyadh. These subjects were reclassified to cigarette smokers (n=19), water pipe smokers (n=5) and non-smokers (n=27). The study also investigated the intake of macronutrients and selected micronutrients. In addition, the study investigated other health indicators including Body Mass Index (BMI), hematocrit, hemoglobin, plasma alkaline phosphatase activity and albumin concentration, urinary creatinine and urea nitrogen excretion. The mean of vitamin B-6 intake, B-6 to protein ratio, plasma pyridoxal phosphate (PLP) concentration and urinary 4-PA excretion in urban group were 2.18 ± 0.62 mg/day, 0.022 ± 0.008 mg/g, 39.3 ± 18.0 nmol/L and 4.6 ± 2.3 μmol/day, respectively. In rural group, these measures were 2.15 ± 0.65 mg/day, 0.021 ± 0.004 mg/g, 40.5 ± 14.6 nmol/L and 4.4 ± 2.3 (μmol/day, respectively. These measures indicated adequate status with no significant difference between the two groups. The mean intake of calcium, folate, vitamin D, zinc and dietary fiber was lower than recommendation of the Dietary Reference Intakes (DRI) in both groups. Health indicators were within normal range except for BMI, which indicated a prevalence of overweight and obesity in both urban (27.1 ± 5.5 Kg/m²) and rural (28.2 ± 6.0 Kg/m²) subjects. Comparison of the three smoking groups showed that the water pipe smokers compared to cigarette smokers and non-smokers groups had significantly higher mean intake of vitamin B-6 (2.51 ± 0.73 mg/day), which resulted in higher concentrations of plasma PLP, pyridoxal (PL), red blood cells PLP and urinary 4-PA (54.9 ± 23.1 nmol/L, 21.5 ± 10.0 nmol/L, 33.7 ± 8.5 nmol/L and 6.9 ± 4.7 μmol/day, respectively). Cigarette smokers had significantly lower concentration of plasma PLP (30.9 ± 12.5 nmol/L) compared to non-smokers (40.0 ± 12.9 nmol/L) without a significant difference in vitamin B-6 intake. Hematocrit and hemoglobin were significantly higher in smokers (50 ± 3% and 167 ± 11 g/L, respectively) compared to non-smokers (48 ± 3% and 160 ± 9 g/L, respectively). The results of this study suggest that vitamin B-6 status of adult males in Riyadh is adequate with no urban vs. rural variation. / Graduation date: 2004

[Truncated abstract] An elevated total plasma homocysteine concentration (tHcy) is associated with an increased risk of myocardial infarction and ischemic stroke. Folic acid, vitamin B6 and B12 supplements significantly reduce tHcy even in people who are not overtly vitamin deficient. If homocysteine is a causal risk factor for atherothrombotic events, treatment with B-vitamins might prove a simple and cost-effective means to reduce cardiovascular risk. However, it remains unclear whether elevated tHcy causes atherosclerosis or is simply a risk marker. To prove that homocysteine is a modifiable risk factor for cardiovascular disease it is necessary to show that lowering tHcy reduces vascular risk. The aim of this study was to determine whether long-term homocysteine-lowering with B-vitamins would improve vascular structure and function in people with a history of stroke. This study was a cross-sectional sub-study of the Vitamins TO Prevent Stroke trial (VITATOPS), a multi-centre, randomised, double-blind, placebo-controlled clinical trial designed to test the efficacy and safety of B-vitamins (folic acid 2mg, vitamin B6 25mg and vitamin B12 0.5mg) in the prevention of vascular events in patients with a recent history of stroke or transient ischemic attack. 173 VITATOPS participants were recruited for the current study. Age, sex, stroke type, medications, cardiovascular risk factors and smoking history were recorded and blood pressure, height, weight, waist and hip girth were measured in all subjects at least two years after randomisation. ... After a mean treatment period of 3.9 ± 0.9 years, the subjects randomised to vitamin treatment had significantly lower tHcy than the subjects randomised to placebo (7.9mol/L, 95%CI 7.5, 8.4 versus 11.8mol/L, 95%CI 10.9, 12.8; p<0.001). There were no significant differences between groups in CIMT (0.84 ± 0.17mm vitamins versus 0.83 ± 0.18mm placebo; p=0.74) or FMD (median of 4.0%, IQR 0.9, 7.2, vitamins versus 3.0%, IQR 0.6, 6.6 placebo; p=0.48). Pooled estimates from the meta-analyses showed that B-vitamin treatment reduces CIMT by 0.10mm (95%CI –0.20, -0.01mm) and increases FMD by 1.4%, (95%CI 0.7, 2.2), although these estimates may have been influenced by positive publication bias. The improvement in FMD was significant in studies of less than eight weeks duration but not in studies with longer treatment periods. The association between tHcy and CIMT and FMD was eliminated by adjustment for renal function and long-term B-vitamin treatment did not alter the strong linear relationship between tHcy and cystatin C. Lowering tHcy did not alter arterial wall inflammation assessed by 18FDG-PET, although small subject numbers meant we were unable to exclude a minor treatment effect. Long-term homocysteine-lowering with B-vitamin treatment did not improve CIMT or FMD or reduce arterial wall inflammation in people with a history of stroke. The relationship between tHcy and these markers of vascular risk was eliminated by adjustment for renal function. Our data are consistent with the hypothesis that elevated tHcy is a risk marker for cardiovascular disease rather than a modifiable causal risk factor.

Tesis por compendio / [ES] Enmarcada en la línea de investigación de nuestro laboratorio sobre señalización por nitrógeno principalmente en la cianobacteria Synechococcus elongatus PCC7942, con esfuerzos centrados en las proteínas PII y PipX y su red de señalización, esta Tesis amplía el espectro de moléculas investigadas en relación con dicha red. Estudia y caracteriza el miembro no canónico de la superfamilia de la proteína PII denominado CutA, generalmente anotado como de protección frente a metales divalentes, altamente conservado en todos los dominios de la vida (incluidos animales y el ser humano). En ella examinamos la posible protección frente a metales provista por CutA en dos bacterias muy distantes, Escherichia coli y Synechococcus elongatus, usando knockouts para ambas del gen que codifica para CutA. Ni los estudios de complementación en E. coli del gen silvestre ni los observacionales de sensibilidad a metales en S. elongatus han dado soporte a la función anotada para CutA, a pesar de que demostramos mediante seguimiento turbidimétrico que el Cu2+ hace agregar a la proteína CutA pura de S. elongatus (producida recombinantemente) y por tanto se une a ella, aunque con una afinidad baja por comparación con las concentraciones tóxicas de este metal para dicha cianobacteria. Buscando profundizar en el conocimiento de CutA, hemos determinado a muy alta resolución mediante difracción de rayos X la estructura de esta proteína de S. elongatus, sin evidenciar complejo alguno con cobre, pero demostrando que los tres bolsillos intersubunidades en el homotrímero de CutA son capaces de transportar moléculas orgánicas (en nuestro caso Bis-Tris). Estos resultados apoyan una posible función de CutA basada en la unión a estos bolsillos de biomoléculas neutras o positivamente cargadas y capaces de formar varios puentes de hidrógeno con las paredes de potencial negativo y fuerte carácter polar de estos bolsillos. También hemos estudiado la proteína PipY de S. elongatus, identificada recientemente como pareja funcional de la antes mencionada PipX, determinando sus propiedades espectroscópicas, unión de piridoxal fosfato (PLP) y resolviendo su estructura mediante difracción de rayos X. Probamos que PipY es monomérica y que tiene PLP unido. Su estructura no apoya que sea un enzima, siendo aparentemente apropiada para ejercer una posible función en la homeostasis de PLP. Dado que muy recientemente se ha descrito una epilepsia genética humana dependiente de vitamina B6 debida a mutaciones en el gen humano ortólogo de pipY, PROSC (ahora llamado PLPBP; codifica la proteína PLPHP), usamos inicialmente PipY de S. elongatus y luego PROSC humana como banco de pruebas de la patogenicidad de las mutaciones que se han asociado a esta epilepsia, utilizando para ello mutagénesis dirigida y producción de las formas silvestre y mutantes de estas proteínas, comparando sus propiedades. Estos estudios han demostrado la patogenicidad y establecido mecanismos para la misma para cada una de las mutaciones de cambio de sentido de PROSC descritas hasta ahora en esta epilepsia. Nuestros estudios han representado un importante avance en la comprensión de las proteínas de tipo PipY y de la epilepsia asociada a la forma humana de las mismas. / [CA] Emmarcada en la línia d'investigació del nostre laboratori de senyalització per nitrogen principalment en el cianobacteri Synechococcus elongatus PCC7942, amb esforços centrats en les proteïnes PII i PipX i la seua xarxa de senyalització, esta Tesi amplia l'espectre de molècules investigades en relació amb la dita xarxa. Estudia i caracteritza el membre no canònic de la superfamília de la proteïna PII denominat CutA, generalment anotat com de protecció a metalls divalents, altament conservat en tots els dominis de la vida (inclosos animals i l'ésser humà). En ella examinem la possible protecció front a metalls proveïda per CutaA en dos bacteris molt distants, Escherichia coli i Synechococcus elongatus, usant knockouts del gen que codifica CutA per a ambdues. Ni els estudis de complementació en E. coli del gen silvestre ni els observacionals de sensibilitat a metalls en S. elongatus han donat suport a la funció anotada per CutA, tot i que vam demostrar mitjançant seguiment turbidimétric que el Cu2 + fa agregar a la proteïna CutA pura de S. elongatus (produïda de forma recombinant) i per tant s'uneix a ella, encara que amb una afinitat baixa per comparació amb les concentracions tòxiques d'aquest metall per a aquest cianobacteri. Buscant aprofundir en el coneixement de CutA, hem determinat a molt alta resolució mitjançant difracció de raigs X l'estructura d'aquesta proteïna de S. elongatus, sense evidenciar cap complex amb coure, però demostrant que les tres cavitats formades entre les subunitats del homotrimer de CutA són capaços de transportar molècules orgàniques (en el nostre cas Bis-Tris). Aquests resultats donen suport a una possible funció de CutA basada en la unió a aquestes cavitats de biomolècules neutres o positivament carregades i capaços de formar diversos ponts d'hidrogen amb les parets de potencial negatiu i fort caràcter polar d'aquestes cavitats. També hem estudiat la proteïna PipY de S. elongatus, identificada recentment com a parella funcional de l'abans esmentada PipX, determinant les seves propietats espectroscòpiques, unió de piridoxal fosfat (PLP) i resolent la seva estructura mitjançant difracció de raigs X. Vam provar que PipY és monomèrica i que té PLP unit. La seva estructura no recolza que sigui un enzim, sent aparentment apropiada per a exercir una possible funció en l'homeòstasi de PLP. Atès que molt recentment s'ha descrit una epilèpsia genètica humana dependent de vitamina B6 deguda a mutacions en el gen humà ortòleg de pipY, PROSC (ara anomenat PLPBP; codifica la proteïna PLPHP), fem servir inicialment PipY de S. elongatus i després PROSC humana com banc de proves de la patogenicitat de les mutacions que s'han associat a aquesta epilèpsia, utilitzant mutagènesi dirigida i produint les formes silvestre i mutants d'aquestes proteïnes, comparant les seves propietats. Aquests estudis han demostrat la patogenicitat i establert mecanismes per a la mateixa per a cadascuna de les mutacions de canvi de sentit de PROSC descrites fins ara en aquesta epilèpsia. Els nostres estudis han representat un important avanç en la comprensió de les proteïnes de tipus PipY i de l'epilèpsia associada a la forma humana de les mateixes. / [EN] In the context of research of our laboratory on nitrogen signaling mainly in the cyanobacterium Synechococcus elongatus PCC7942, with efforts focused on the PII and PipX proteins and their signaling network, this Thesis extends the spectrum of molecules investigated in relation to such network. It studies and characterizes the non-canonical member of the PII protein superfamily named CutA, a highly conserved protein in all domains of life (including animals and humans) which is generally annotated as protecting against divalent metals. We examine the possible protection provided by CutA against metals, using knockouts for the CutA-encoding gene of two phylogenetically distant bacteria, Escherichia coli and Synechococcus elongatus PCC7942. Neither complementation studies in E. coli by the wild-type gene, nor observational studies of sensitivity to metals in the S. elongatus knockout have supported the function annotated for CutA, although we show by turbidimetric monitoring that Cu2+ causes aggregation of pure S. elongatus CutA (produced recombinantly) and therefore binds to it, although with a low affinity by comparison with the concentrations of this metal that are toxic for this cyanobacterium. Aiming at getting further insight into CutA, we have determined at very high resolution, by X-ray diffraction, the structure of this protein of S. elongatus, failing to observe Cu2+ bound in this structure, but showing that the three pockets formed at intersubunit boundaries in the CutA homotrimer are capable of transporting organic molecules (in our case Bis-Tris) without inducing conformational changes in the protein. This finding supports a possible function of CutA based on the binding to these pockets of neutral or positively charged biomolecules capable of forming several hydrogen bonds with the pocket walls, which are endowed with negative potential and have a strong polar character. We have also studied the PipY protein of S. elongatus, recently identified as a functional partner of the aforementioned PipX, determining its spectroscopic properties, binding of pyridoxal phosphate (PLP) and solving its structure by X-ray diffraction. We prove that PipY is monomeric and has PLP attached. Its structure does not favor an enzymatic role of PipY, being more appropriate for exerting a possible function in the homeostasis of PLP. Given the very recent description of a human vitamin B6-dependent genetic epilepsy associated to mutations in the human orthologue of the pipY gene, PROSC (now called PLPBP, encoding the PROSC protein, now named PLPHP), we used first S. elongatus PipY and afterwards and more extensively human PROSC to test by site-directed mutagenesis the pathogenicity of the mutations that have been associated with this epilepsy. These studies have demonstrated the pathogenicity and established mechanisms for this pathogenicity for each of the missense mutations reported thus far in patients with PROSC-associated epilepsy. Our studies represent an important advance in the understanding of PipY-like proteins and of epilepsy associated with the human form thereof. / Para la realización de esta Tesis, Lorena Tremiño Agulló ha disfrutado de una Beca de Formación de Personal Investigador (FPI) (BES-2012-058304) otorgado por el Ministerio de Economía, Industria y Competitividad. El trabajo se ha llevado a cabo en el grupo 739 del CIBERER-Instituto de Salud Carlos III (IP, V. Rubio) y se ha enmarcado dentro de los proyectos: -“Luz estructural sobre señalización y regulación por nitrógeno y sobre biosíntesis de arginina/urea, sus errores congénitos, y su conexión con biología del envejecimiento”, (BFU2011-30407) del Ministerio de Economía y Competitividad del Gobierno de España (Investigador principal,V. Rubio). -“Una mirada molecular al control de la detoxificación de amonio y a sus patologías y errores congénitos, y a la señalización por amonio. En busca del papel de la proteína CutA”, (BFU2014-58229) del Ministerio de Economía y Competitividad del Gobierno de España (Investigador principal, V. Rubio). -"BioMeder. Genes, proteínas y rutas de señalización en enfermedades raras" (PrometeoII/2014/029) de la Conselleria d'Educació de la Generalitat Valenciana (investigadores, P. Sanz, A. Marina y V. Rubio). / Tremiño Agulló, L. (2019). Bases estructurales de la señalización y regulación por nitrógeno y procesos asociados [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/117999 / TESIS / Compendio

ABSTRACT The porphyrias are a diverse group of metabolic disorders arising from diminished activity of enzymes in the heme biosynthetic pathway. They can present with acute neurovisceral symptoms, cutaneous symptoms, or both. The complexity of these disorders is demonstrated by the fact that some acute porphyria patients with the underlying genetic defect(s) are latent and asymptomatic while others present with severe symptoms. This indicates that there is at least one other risk factor required in addition to the genetic defect for symptom manifestation. A systematic review of the heme biosynthetic pathway highlighted the involvement of a number of micronutrient cofactors. An exhaustive review of the medical literature uncovered numerous reports of micronutrient deficiencies in the porphyrias as well as successful case reports of treatments with micronutrients. Many micronutrient deficiencies present with symptoms similar to those in porphyria, in particular vitamin B6. It is hypothesized that a vitamin B6 deficiency and related micronutrient deficiencies may play a major role in the pathogenesis of the acute porphyrias. In order to further investigate the porphyrias, a computational model of the heme biosynthetic pathway was developed based on kinetic parameters derived from a careful analysis of the literature. This model demonstrated aspects of normal heme biosynthesis and illustrated some of the disordered biochemistry of acute intermittent porphyria (AIP). The testing of this model highlighted the modifications necessary to develop a more comprehensive model with the potential to investigated hypotheses of the disordered biochemistry of the porphyrias as well as the discovery of new methods of treatment and symptom control. It is concluded that vitamin B6 deficiency might be the risk factor necessary in conjunction with the genetic defect to trigger porphyria symptoms.