Exogenous Nutrients Research Articles

Improved production of ethanol using bagasse from different sorghum cultivars

For improved production of ethanol from whole sorghum residues, physico-chemical compositions and fermentation characteristics of the substrates are important factors to consider. In the present study, Nigerian sorghum cultivars SSV2, KSV8 and KSV3 were grown under rain-fed conditions without chemical fertilization in Kano state, Nigeria. On harvest, the whole sorghum residues (bagasse) comprising crushed stalks, leaves, panicles and peduncles were collected for further processing. Bagasse samples, which had different macromolecular composition and carbohydrate pasting properties, were pre-treated with dilute sulphuric acid at 75 °C followed by enzymatic hydrolysis and sequential detoxification by Ca(OH)2 over-liming and charcoal filtration. Hydrolysate samples were subsequently fermented with the yeasts, Saccharomyces cerevisiae and Pachysolen tannophilus. Sugar consumption, carbon dioxide evolution and ethanol production were shown to vary depending on the sorghum cultivar type. While KSV3 yielded most favourable biomass of 37 t ha−1 (dry basis), bagasse from cultivar SSV2 yielded the most favourable level of sugars (69 g/100 g) after enzymatic hydrolysis, and also consistently exhibited improved fermentation performance. Detoxification of pre-treated sorghum bagasse to remove potential yeast inhibitors resulted in improvement in ethanol yield, with 23 g L−1 ethanol (representing 72% of theoretical yield) being achieved from SSV2 bagasse following fermentation with P. tannophilus without exogenous nutrient supplementation. Our findings reveal that the choice of sorghum cultivar is important when converting bagasse to ethanol, and further that pretreatment with dilute acid at moderate temperature followed by detoxification improves fermentation kinetics and ethanol yield.

Effects of exogenous nutrients on polyketide biosynthesis in Escherichia coli.

Heterologous hosts are important platforms for engineering natural product biosynthesis. Escherichia coli is such a host widely used for expression of various biosynthetic enzymes. While numerous studies have been focused on optimizing the expression conditions for desired functional proteins, this work describes how supplement of exogenous nutrients into the fermentation broth influences the formation of natural products in E. coli. A type III polyketide synthase gene stts from Streptomyces toxytricini NRRL 15443 was heterogeneously expressed in E. coli BL21(DE3). This enzyme uses five units of malonyl-CoA to generate a polyketide 1,3,6,8-tetrahydroxynaphthalene, which can be spontaneously oxidized into a red compound flaviolin. In this work, we manipulated the fermentation broth of E. coli BL21(DE3)/pET28a-stts by supplying different nutrients including glucose and sodium pyruvate at different concentrations, from which six flaviolin derivatives 1-6 were produced. While addition of glucose yielded the production of 1-4, supplement of sodium pyruvate into the induced broth of E. coli BL21(DE3)/pET28a-stts resulted in the synthesis of 5 and 6, suggesting that different nutrients may enable E. coli to generate different metabolites. These products were purified and structurally characterized based on the spectral data, among which 2-6 are novel compounds. These molecules were formed through addition of different moieties such as acetone and indole to the flaviolin scaffold. The concentrations of glucose and sodium pyruvate and incubation time affect the product profiles. This work demonstrates that supplement of nutrients can link certain intracellular metabolites to the engineered biosynthetic pathway to yield new products. It provides a new approach to biosynthesizing novel molecules in the commonly used heterologous host E. coli.

Metabolic engineering of a glycerol-oxidative pathway in Lactobacillus panis PM1 for utilization of bioethanol thin stillage: potential to produce platform chemicals from glycerol.

Lactobacillus panis PM1 has the ability to produce 1,3-propanediol (1,3-PDO) from thin stillage (TS), which is the major waste material after bioethanol production, and is therefore of significance. However, the fact that L. panis PM1 cannot use glycerol as a sole carbon source presents a considerable problem in terms of utilization of this strain in a wide range of industrial applications. Accordingly, L. panis PM1 was genetically engineered to directly utilize TS as a fermentable substrate for the production of valuable platform chemicals without the need for exogenous nutrient supplementation (e.g., sugars and nitrogen sources). An artificial glycerol-oxidative pathway, comprised of glycerol facilitator, glycerol kinase, glycerol 3-phosphate dehydrogenase, triosephosphate isomerase, and NADPH-dependent aldehyde reductase genes of Escherichia coli, was introduced into L. panis PM1 in order to directly utilize glycerol for the production of energy for growth and value-added chemicals. A pH 6.5 culture converted glycerol to mainly lactic acid (85.43 mM), whereas a significant amount of 1,3-propanediol (59.96 mM) was formed at pH 7.5. Regardless of the pH, ethanol (82.16 to 83.22 mM) was produced from TS fermentations, confirming that the artificial pathway metabolized glycerol for energy production and converted it into lactic acid or 1,3-PDO and ethanol in a pH-dependent manner. This study demonstrates the cost-effective conversion of TS to value-added chemicals by the engineered PM1 strain cultured under industrial conditions. Thus, application of this strain or these research findings can contribute to reduced costs of bioethanol production.

The general amino acid control pathway regulates mTOR and autophagy during serum/glutamine starvation

Organisms have evolved elaborate mechanisms to adjust intracellular nutrient levels in response to fluctuating availability of exogenous nutrients. During starvation, cells can enhance amino acid uptake and synthesis through the general amino acid control (GAAC) pathway, whereas nonessential cellular contents are recycled by autophagy. How these two pathways are coordinated in response to starvation is currently unknown. Here we show that the GAAC pathway couples exogenous amino acid availability with autophagy. Starvation caused deactivation of mTOR, which then activated autophagy. In parallel, serum/glutamine starvation activated the GAAC pathway, which up-regulated amino acid transporters, leading to increased amino acid uptake. This elevated the intracellular amino acid level, which in turn reactivated mTOR and suppressed autophagy. Knockdown of activating transcription factor 4, the major transcription factor in the GAAC pathway, or of SLC7A5, a leucine transporter, caused impaired mTOR reactivation and much higher levels of autophagy. Thus, the GAAC pathway modulates autophagy by regulating amino acid uptake and mTOR reactivation during serum/glutamine starvation.

Thermal acclimation and nutritional history affect the oxidation of different classes of exogenous nutrients in Siberian hamsters, Phodopus sungorus.

During acclimatization to winter, changes in morphology and physiology combined with changes in diet may affect how animals use the nutrients they ingest. To study (a) how thermal acclimation and (b) nutritional history affect the rates at which Siberian hamsters (Phodopus sungorus) oxidize different classes of dietary nutrients, we conducted two trials in which we fed hamsters one of three (13) C-labeled compounds, that is, glucose, leucine, or palmitic acid. We predicted that under acute cold stress (3 hr at 2°C) hamsters previously acclimated to cold temperatures (10°C) for 3 weeks would have higher resting metabolic rate (RMR) and would oxidize a greater proportion of dietary fatty acids than animals acclimated to 21°C. We also investigated how chronic nutritional stress affects how hamsters use dietary nutrients. To examine this, hamsters were fed four different diets (control, low protein, low lipid, and low-glycemic index) for 2 weeks. During cold challenges, hamsters previously acclimated to cold exhibited higher thermal conductance and RMR, and also oxidized more exogenous palmitic acid during the postprandial phase than animals acclimated to 21°C. In the nutritional stress trial, hamsters fed the low protein diet oxidized more exogenous glucose, but not more exogenous palmitic acid than the control group. The use of (13) C-labeled metabolic tracers combined with breath testing demonstrated that both thermal and nutritional history results in significant changes in the extent to which animals oxidize dietary nutrients during the postprandial period.

Duodenal Luminal Chemosensing; Acid, ATP, and Nutrients

Intestinal chemosensing of endogenous and exogenous luminal compounds, including acid, CO2, bile acids and nutrients is an emerging area of gastrointestinal research, since gut hormones, particularly including incretins and glucagon-like peptide-2 (GLP-2) are released in response to luminal nutrients. Identification of luminal chemosensors such as nutrient-ligand G-protein coupled receptors (GPCRs) in enteroendocrine cells has linked luminal compounds to the corresponding gut hormone release. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption, and motility. We have been studying the mechanisms by which luminal compounds are sensed via mucosal acid sensors and GPCRs, which trigger mucosal defense mechanisms. In addition to luminal acid/CO2 sensing in the duodenum, recent studies also show that compounds present post-prandially such as amino acids, bile acids and fatty acids, enhance duodenal mucosal defenses, with digestion following the initial gastric processing. These studies may form the basis for therapies in which luminal nutrients release gut hormones that affect the mucosal protection, appetite, satiety, and systemic metabolisms.

A comparative study of ethanol production using dilute acid, ionic liquid and AFEX™ pretreated corn stover.

BackgroundIn a biorefinery producing cellulosic biofuels, biomass pretreatment will significantly influence the efficacy of enzymatic hydrolysis and microbial fermentation. Comparison of different biomass pretreatment techniques by studying the impact of pretreatment on downstream operations at industrially relevant conditions and performing comprehensive mass balances will help focus attention on necessary process improvements, and thereby help reduce the cost of biofuel production.ResultsAn on-going collaboration between the three US Department of Energy (DOE) funded bioenergy research centers (Great Lakes Bioenergy Research Center (GLBRC), Joint BioEnergy Institute (JBEI) and BioEnergy Science Center (BESC)) has given us a unique opportunity to compare the performance of three pretreatment processes, notably dilute acid (DA), ionic liquid (IL) and ammonia fiber expansion (AFEXTM), using the same source of corn stover. Separate hydrolysis and fermentation (SHF) was carried out using various combinations of commercially available enzymes and engineered yeast (Saccharomyces cerevisiae 424A) strain. The optimal commercial enzyme combination (Ctec2: Htec2: Multifect Pectinase, percentage total protein loading basis) was evaluated for each pretreatment with a microplate-based assay using milled pretreated solids at 0.2% glucan loading and 15 mg total protein loading/g of glucan. The best enzyme combinations were 67:33:0 for DA, 39:33:28 for IL and 67:17:17 for AFEX. The amounts of sugar (kg) (glucose: xylose: total gluco- and xylo-oligomers) per 100 kg of untreated corn stover produced after 72 hours of 6% glucan loading enzymatic hydrolysis were: DA (25:2:2), IL (31:15:2) and AFEX (26:13:7). Additionally, the amounts of ethanol (kg) produced per 100 kg of untreated corn stover and the respective ethanol metabolic yield (%) achieved with exogenous nutrient supplemented fermentations were: DA (14.0, 92.0%), IL (21.2, 93.0%) and AFEX (20.5, 95.0%), respectively. The reason for lower ethanol yield for DA is because most of the xylose produced during the pretreatment was removed and not converted to ethanol during fermentation.ConclusionsCompositional analysis of the pretreated biomass solids showed no significant change in composition for AFEX treated corn stover, while about 85% of hemicellulose was solubilized after DA pretreatment, and about 90% of lignin was removed after IL pretreatment. As expected, the optimal commercial enzyme combination was different for the solids prepared by different pretreatment technologies. Due to loss of nutrients during the pretreatment and washing steps, DA and IL pretreated hydrolysates required exogenous nutrient supplementation to ferment glucose and xylose efficiently, while AFEX pretreated hydrolysate did not require nutrient supplementation.

Protocol to compensate net evaporation and net precipitation in open-pond microalgal massive cultures and permit maximal steady-state productivities

Commercial cultivation of microalgae in open ponds can be strongly limited by evaporation. This is particularly the case in highly evaporative areas where production plants are likely to be located. We present a mathematical model to calculate native solute and exogenous nutrient concentrations as affected by net evaporation or net precipitation. The model takes into account the periodic compensatory addition of new feedstock water and/or removal of rain-originated excess water and the eventual recycling of the culture medium. We present a management protocol in which, for a wide variety of climates, it is possible to stabilise the native solute concentrations and minimise the exogenous nutrient washout. The protocol includes harvesting a minimum of 10% of the pond volume per day and replacing this volume and the evaporated water with new feedstock water. We test the approach against a 9-year daily weather data set for a locality with 1740 mm.y−1 average net evaporation. We find that the native solute concentrations can be maintained between 1.2 and 1.5 times the feedstock water values, while the daily washout of exogenous nutrients is ≤3% and the pond volume is kept nearly constant. This protocol should prove particularly useful for the exploitation of marine microalgae growing in open ponds with brackish or seawater-based growth medium.

The marriage of nutrigenomics with the microbiome: the case of infant-associated bifidobacteria and milk

Broadly, nutrigenomics examines the association of exogenous nutrients and molecular responses to maintain homeostasis in an individual. Phenotypic expression profiling, often transcriptomics, has been applied to identify markers and metabolic consequences of suboptimal diet, lifestyle, or both. The decade after the Human Genome Project has been marked with advances in high-throughput analysis of biological polymers and metabolites, prompting a rapid increase in characterization of the profound nature by which our symbiotic microbiota influences human physiology. Although the technology is widely accessible to assess microbiome composition, genetic potential, and global function, nutrigenomics studies often exclude the microbial contribution to host responses to ingested nutritive molecules. Perhaps a hallmark of coevolution, milk provides a dramatic example of a diet that promotes a particular microbial community structure, because the lower infant gastrointestinal tract is often dominated by bifidobacteria that flourish on milk glycans. Systems-level approaches should continue to be applied to examine the microbial communities in the context of their host's dietary habits and metabolic status. In addition, studies of isolated microbiota species should be encouraged to inform clinical studies and interventions as well as community studies. Whereas nutrigenomics research is beginning to account for resident microbiota, the need remains to consistently consider our microscopic partners in the human holobiont.

Sepsis in the Central Nervous System and Antioxidant Strategies with Nacetylcysteine, Vitamins and Statins

Sepsis is the complex syndrome characterized by an imbalance between proinflammatory and antiinflammatory response to infection. The brain may be affected during the sepsis, and acute and long-term brain dysfunctions have been observed in both animal models and septic patients. Oxidative stress and antioxidant systems may prove the basis underling brain dysfunction in sepsis. The antioxidant therapy may be theoretically achieved by the following strategies: restoring endogenous antioxidants and nutrients and supplementation with exogenous trace elements, vitamins, and nutrients with antioxidant proprieties; or administering drugs that reduce oxidative stress, such as N-acetylcysteine (NAC), vitamins and statins. In the review, we described below the involvement of oxidative stress and antioxidants defenses and potential utility of these strategies and present data regarding their use in sepsis.

Microbiome analysis of a microalgal mass culture growing in municipal wastewater in a prototype OMEGA photobioreactor

Large-scale cultivation of microalgae for biofuels may avoid competing for agriculture, water, and fertilizer by using wastewater and avoid competing for land by using the Offshore Membrane Enclosures for Growing Algae (OMEGA) system. Some microalgae thrive in wastewater; however, wastewater also contains a complex mixture of organisms. An algae culture in wastewater from a San Francisco Treatment Facility in a 1600-L OMEGA culture system was monitored by standard methods. Prima facie evidence of a chytrid infection prompted a detailed investigation of the microbiome over a 13-day period using second generation sequencing of hypervariable regions of the small subunit rRNA genes. The observed bacteria, initially dominated by γ-proteobacteria, shifted to Cytophagia, Flavobacteriia, and Sphingobacteriia after addition of exogenous nutrients. The dominant algae genera introduced with the inoculum, Desmodesmus and Scenedesmus, remained over 70% of the sequence reads on day 13, although the optical density and fluorescence of the culture declined. Nonalgal eukarya, initially dominated by unclassified alveolates, chrysophytes, and heliozoan grazers, shifted to chytrid fungi on day 5 and continued to day 13. The results of this microbiome analysis can facilitate the development of probe or primer based surveillance systems for routine monitoring of large-scale microalgae cultures.

Induction of a Stringent Metabolic Response in Intracellular Stages of Leishmania mexicana Leads to Increased Dependence on Mitochondrial Metabolism

Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using 13C-stable isotope resolved metabolomics and 2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate) and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA) cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.

Exogenous nutrient manipulations alter endogenous extractability of carbohydrates in decomposing foliar litters under a typical mixed forest of subtropics

Litter decomposition is a major driver of nutrient availability and carbon (C) cycling in forest ecosystems, and may be susceptible to perturbation by exogenous nutrient inputs from anthropogenic activity. The role of resource limitation in this process is unclear, although some models suggest the macronutrients nitrogen (N) and phosphorus (P) stimulate early-stage decomposition while availability of labile C restricts later-stage decomposition. We studied this interplay in a subtropical mixed forest in southern China through in situ incubations of litter samples over a 540-day period. Litter samples were amended with labile C (+C, as sucrose), N (+N, as NH4NO3), P (+P, as NaH2PO4), all three inputs (+CNP), or no inputs (CK). Litter mass and nutrient content were measured at 90-day intervals, while extractable carbohydrate profiles of the litter samples were assayed at 90, 270, and 450days of incubation. The +P and +CNP treatments showed greater reductions in litter mass, as well as a larger P pool throughout the incubation. The +N treatment had a larger N pool, but otherwise did not differ from the no input control CK. The concentration of accessible carbohydrate fractions remained constant or increased from 90 to 450days of incubation, while less accessible fractions thought to be lignocellulose and hemi-cellulose decreased during that period. Total extractable carbohydrates decreased in the +P treatment, but was not significantly different among other treatments. Our results suggest that mixed forest systems in southern China are likely to be minimally perturbed in the short term by exogenous N addition, and that decomposition activity is not regulated by labile C availability over the time period studied. Moreover, increased C inputs due to climate change-induced changes in litter deposition and root exudation will likely have a smaller impact on subtropical forest management than anthropogenic disturbances such as P fertilization.

Formin homology 1 (OsFH1) regulates submergence-dependent root hair development in rice plants

By using a forward genetic approach, a formin homology 1 gene (OsFH1) was identified as a critical regulator of rice root hair development. The phenotypic effect of OsFH1 on root hair development was verified by using three independent mutants, one point mutation and two T-DNA insertions. The study showed that OsFH1 is required for the elongation of root-hairs. However, Osfh1 exhibited growth defect of root hairs only when roots were grown submerged in solution. To understand how OsFH1 impinges on plant responses to root submergence, the growth responses of Osfh1 root hairs to anoxia, carbohydrate supplementation and exogenous hormones (auxin and ethylene) and nutrients (Fe and Pi) were examined. However, none of these treatments rescued the growth defects of Osfhl1 root hairs. This study demonstrates that OsFH1 could be involved in preventing submergence-induced inhibition of root hair growth.

Kitchen Waste Residues asKitchen Waste Residues as Potential Renewable Biomass Resources for the Production of Multiple Fungal Carbohydrases and Second Generation Bioethanol

Utilization of kitchen waste, the major portion of municipal solid waste for the coproduction of multiple carbohydrases and bioethanol was investigated in this study. Solid-state fermentation was performed to evaluate the potential of various steam pretreated kitchen waste residues as substrates for the coproduction of cellulolytic, hemicellulolytic, pectinolytic, amylolytic enzymes by a locally isolated strain of Aspergillus niger CJ-5. All the kitchen waste residues simply moistened with water, without the supplementation of exogenous nutrients proved good for the induction of all the enzyme components of a cocktail after 96 h incubation. Of all the substrates evaluated, steam pretreated potato peels induced maximum yields corresponding to 69.0±1.92U CMCase, 16.5±0.54U FPase, 44.0±1.28U β-glucosidase, 999.0±28.90U xylanase, 58.2±2.12U mannanase, 120.0±3.72U pectinase, 31520.0±375.78U α-amylase, 482.8±9.82U glucoamylase/g dry substrate (gds). Saccharification of residues using inhouse produced crude enzyme cocktail resulted in the release of 610±10.56, 570±8.89, 435±6.54, 475±4.56, 445±4.27, 385±4.49, 370±6.89, 490±10.45 mg of total reducing sugars/g of dried potato peels, orange peels, pineapple peels, mausami peels, onion peels, banana stalks, pea pods and composite mixture respectively revealing carbohydrate conversion efficiencies in the range of 97.0-99.4%. After fermentation of released hexoses, alcohol yields ranging from 80±1.069 - 262±7.86 µL/gds were obtained.

Strong modulation of nutrient distribution in Alnus glutinosa as a function of the actinorhizal symbiosis

Micro- and macro-nutrient acquisition by plants and microorganisms is a cornerstone for their survival and has a direct impact on biogeochemical cycling. In this study, we investigated, in controlled conditions, how the availability of exogenous nitrate impacted nutrient acquisition and distribution in black alder (Alnus glutinosa (L.) Gaertn.) in the presence, or absence, of its nitrogen-fixing bacterial symbiont (Frankia sp.). Our findings show that alder physiology and distribution of nutrients between aerial and root tissues were strongly influenced by the presence of the symbiont. In both nodulated and non-nodulated alders, root allocation and total plant biomass were positively correlated, except when nodulated alders were subjected to low nitrate conditions (≤15 ppm). Alders receiving 45 ppm exogenous nitrate had a less developed actinorhizal symbiosis. These findings reflect the importance of root exploration in relation to plant dependence to exogenous nitrate. Nutrient composition of alder aerial tissues, in particular molybdenum, was significantly altered in the presence of Frankia. In the context of plant leaf-litter mutualism involving metals and N exchange, our findings of high Mo and P translocation to shoots of non-nodulated alders underscores how the state of the symbiosis in actinorhizal plants can influence the biogeochemical cycling of elements.

Improving the representation of internal nutrient recycling with phosphorus mass balance models: A case study in the Bay of Quinte, Ontario, Canada

We evaluate the relative importance of the causal connection between exogenous total phosphorus (TP) loading and internal nutrient recycling with the water quality conditions in the Bay of Quinte, Ontario, Canada. First, we examine the temporal trends of all the major point and non-point loading sources over the last four decades. We then enhance the mechanistic foundation of an existing simple mass-balance total phosphorus (TP) model, originally developed to guide the eutrophication management in the system. The structural improvements include the incorporation of macrophyte dynamics, the explicit representation of the role of dreissenids in the system, and the improved portrayal of the interplay between water column and sediments. The upgraded model was in good agreement with the observed TP variability in the system during the study period (2002–2009) and successfully reproduced the TP accumulation patterns toward the end of the summer-early fall. We provide evidence that phosphorus dynamics in the upper Bay are predominantly driven by the inflows from Trent River, while the middle and lower segments likely receive substantial internal subsidies from the sediment diagenesis mechanisms and/or the activity of macrophytes and dreissenids (e.g., pseudofeces production, nutrient pump effect). We also forced the model with scenarios of reduced nutrient loading and examine the likelihood of the system to meet its water quality delisting targets, although we caution that our complex overparameterized modeling construct is primarily intended for heuristic purposes. The present study together with the companion paper by Zhang et al. (2013) illustrate how phosphorus mass balance models can offer useful tools for improving our understanding of freshwater ecosystems.

Metabolic Effects of L-carnitine on Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis

Carnitine is an endogenous metabolite and exogenous nutrient with a pivotal role in lipid metabolism. Plasma levels of carnitine are reduced in type 2 Diabetes Mellitus (T2DM). The aim was to evaluate the metabolic effects of the administration of L-carnitine in T2DM. A systematic review was performed. Relevant randomized, controlled-trials trials were searched in Pubmed, Trip Database and Cochrane Library, and selected when they had enough methodological quality assessed with the Jadad scale. Article search strategy included "Carnitine" OR "L-carnitine" AND "Diabetes -Mellitus" OR "Diabetes mellitus, type 2" OR "Noninsulindependent-diabetes mellitus". Meta-analysis was performed, and the difference of means calculated with a 95% confidence interval. Heterogeneity was evaluated with the Q statistic. The systematic review included 4 trials with 284 patients. Oral L-carnitine lowered fasting plasma glucose [-14.3 mg/dl (CI95% - 23.2 to -5.4); p=0,002], total cholesterol [-7.8 mg/dL (95%CI -15.5 to -0.1); p=0.09], low density lipoprotein [-8.8 mg/dl (CI95% -12.2 to -8.5), p<0.0001], apolipoprotein-B100 [-7.6 mg/dl (CI95% -13.6 to -1.6); p=0.013] and apolipoprotein-A1 [-6.0 mg/dl (CI95% -10.5 a -1.5); p=0.523]. There was no significant heterogeneity. The changes in triglycerides, lipoprotein (a) or HbA(1c) were not significant. The administration of L-carnitine in type 2 diabetes mellitus is associated with an improvement in glycaemia and plasma lipids.

Allocation of nutrients to reproduction at high latitudes: Insights from two species of sympatrically nesting geese

ABSTRACT. Understanding factors that determine sources of nutrients for reproduction is vital to interpreting different life history strategies used among species, within species, and among taxa. We used stable carbon isotope analysis (δ13C) to compare the relative use of endogenous and exogenous nutrients during egg synthesis between two species of geese, Canada Geese (Branta canadensis interior) and Lesser Snow Geese (Chen caerulescens caerulescens), nesting on Akimiski Island, Nunavut. We estimated that Canada Geese used 49 ± 1.1% (SE), 61 ± 1.3%, and 51 ± 1.1% endogenous nutrients for albumen, yolk protein, and yolk lipid, respectively. Lesser Snow Geese used significantly less endogenous nutrients during clutch formation, allocating only 25 ± 1.2%, 36 ± 1.5%, and 34 ± 1.7% endogenous nutrients for albumen, yolk protein, and yolk lipid, respectively. Although the proportion of endogenous nutrients allocated to eggs did not vary by year in Canada Geese, proportions varied significantly among years in S...

Investigating xylose metabolism in recombinant Saccharomyces cerevisiae via 13C metabolic flux analysis.

BackgroundTo engineer Saccharomyces cerevisiae for efficient xylose utilization, a fungal pathway consisting of xylose reductase, xylitol dehydrogenase, and xylulose kinase is often introduced to the host strain. Despite extensive in vitro studies on the xylose pathway, the intracellular metabolism rewiring in response to the heterologous xylose pathway remains largely unknown. In this study, we applied 13C metabolic flux analysis and stoichiometric modeling to systemically investigate the flux distributions in a series of xylose utilizing S. cerevisiae strains.ResultsAs revealed by 13C metabolic flux analysis, the oxidative pentose phosphate pathway was actively used for producing NADPH required by the fungal xylose pathway during xylose utilization of recombinant S. cerevisiae strains. The TCA cycle activity was found to be tightly correlated with the requirements of maintenance energy and biomass yield. Based on in silico simulations of metabolic fluxes, reducing the cell maintenance energy was found crucial to achieve the optimal xylose-based ethanol production. The stoichiometric modeling also suggested that both the cofactor-imbalanced and cofactor-balanced pathways could lead to optimal ethanol production, by flexibly adjusting the metabolic fluxes in futile cycle. However, compared to the cofactor-imbalanced pathway, the cofactor-balanced xylose pathway can lead to optimal ethanol production in a wider range of fermentation conditions.ConclusionsBy applying 13C-MFA and in silico flux balance analysis to a series of recombinant xylose-utilizing S. cerevisiae strains, this work brings new knowledge about xylose utilization in two aspects. First, the interplays between the fungal xylose pathway and the native host metabolism were uncovered. Specifically, we found that the high cell maintenance energy was one of the key factors involved in xylose utilization. Potential strategies to reduce the cell maintenance energy, such as adding exogenous nutrients and evolutionary adaptation, were suggested based on the in vivo and in silico flux analysis in this study. In addition, the impacts of cofactor balance issues on xylose utilization were systemically investigated. The futile pathways were identified as the key factor to adapt to different degrees of cofactor imbalances and suggested as the targets for further engineering to tackle cofactor-balance issues.