Hunger and food insecurity can be minimized by doubling crop yield without increasing cultivated land area and fertilizer applied. Since plant breeding has not genetically doubled photosynthesis per unit leaf area, an approach for doubling crop yield would be through a biotechnology that reprograms metabolic pathways in favor of photosynthesis. The anchor of this biotechnology is glutamate dehydrogenase (GDH) including the RNAs it synthesizes. Peanut was treated with stoichiometric combinations of mineral salt solutions to synchronize the GDH subunit polypeptides. Matured seeds were analyzed for fats by HPLC; the RNA biosynthetic activity of GDH, and mRNAs encoding yield-specific enzymes by Northern hybridization. In the PK-treated peanut, the GDH-synthesized RNAs silenced the mRNAs encoding granule-bound starch synthase, phosphoglucomutase (glycolysis), glucosyltransferase (cellulose biosynthesis), and nitrate reductase leaving unaffected the mRNAs encoding acetylcoenzyme A carboxylase (fatty acid biosynthesis), phosphate translocator, and NADH-glutamate synthase resulting to double seed (4342 kg/ha), cellulose (1829 kg/ha), and fat (1381 kg/ha) yields compared with the controls. Down-regulation of phosphate translocator and acetylcoenzyme A carboxylase caused decreased pod yields. GDH-synthesized RNAs that were homologous to yield-specific mRNAs shared extensive plus/plus and plus/minus sequence similarities, and they reprogrammed metabolism by permuting the partially down-regulated, not down-regulated, and down-regulated yield-specific pathways. Control peanut produced 70, NPKS-treated produced 420, NS-treated produced 1680, and PK-treated produced 280 probable rearrangements of the pathways. Therefore, down-regulation of metabolic reactions followed by permutation of yield-related pathways, and redistribution of metabolite load to molecularly connected pathways controls crop yield. Operating as efficient bioreactor, peanut can be maximized to 10000 kg pod/ha, more than enough vegetable oil for nine billion people

Tinsley JH, South S, Chiasson VL, Mitchell BM. Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats. Am J Physiol Regul Integr Comp Physiol 298: R713-R719, 2010. First published January 6, 2010 doi:10.1152/ajpregu.00712.2009.-Hypertensive disorders of pregnancy are characterized by systemic and placental inflammation; however, treatment for these conditions has remained elusive. We tested whether administration of the anti-inflammatory cytokine interleukin-10 (IL-10) during pregnancy would attenuate the hypertension, endothelial dysfunction, proteinuria, and inflammation seen in pregnant DOCA/saline-treated (PDS) rats. Normal pregnant (NP) rats and PDS were given daily intraperitoneal injections of recombinant IL-10 from gestational day 13 until death on day 20. Systolic blood pressure, aortic endothelium-dependent relaxation responses, and urinary protein excretion were measured on days 13 and 20 of gestation. Fetal number and development, plasma endothelin-1 levels, serum and placental levels of IFN␥ and IL-10, and aortic and placental levels of platelet endothelial cell adhesion molecule (PECAM) were assessed on gestational day 20. Systolic blood pressure, aortic endothelial dysfunction, and urinary protein excretion were significantly increased at gestational day 13 in PDS rats. However, all of these were restored to NP levels following IL-10 treatment in PDS rats. IL-10 treatment also significantly increased the number of pups per litter in PDS rats and did not further affect fetal development. The beneficial effects of IL-10 in PDS rats were likely mediated by the decreased plasma levels of endothelin-1, decreased levels of circulating and placental IFN␥, as well as decreased aortic and placental expression of PECAM. These data demonstrate that exogenous IL-10 can normalize blood pressure and endothelial function in pregnancy-induced hypertensive rats and may be beneficial in women with hypertensive disorders of pregnancy. preeclampsia; anti-inflammatory; hypertension; endothelin-1 PREECLAMPSIA (PE), DIAGNOSED as de novo hypertension and proteinuria during pregnancy, and other hypertensive disorders of pregnancy affect ϳ10% of pregnancies in the US and are responsible for 15-20% of maternal deaths worldwide (8). PE is associated with decreased fetal development and increased risk of future maternal heart disease. Although recent scientific findings have greatly aided in explaining the potential mechanisms involved in the development of PE, the exact causes remain unknown and effective treatments for PE remain elusive.Abnormal maternal immune system responses play a key role in the development of PE (10,13,31). A current theory is that women who develop PE have abnormal immunological responses to the fetus and placenta and that the hypertension and proteinuria represent clinical signs of a mild form of fetal rejection, while severe forms of PE result in spontaneous abortion and fetal demise. Consistent with this abnormal immunological response, cli...

Osteoarthritis (OA) is the most common joint disorder in the world and is the most frequent cause of walking related disability among older adults in the US, which brings a significant economic burden and reduces quality of life. The initiation and development of OA typically involves degeneration or progressive loss of the structure and function of articular cartilage. Inflammation is one of the major drives of the progression of OA. Dietary polyphenols have been studied for their anti-inflammatory properties and potential anabolic effects on the cartilage cells. Blueberries are widely consumed and are high in dietary polyphenols, therefore regular consumption of blueberries may help improve OA. The purpose of the present study was to examine the effect of freeze dried whole blueberries on pain, gait performance, and inflammation in individuals with symptomatic knee OA. In a randomized, double-blind trial, adults age 45 to 79 with symptomatic knee OA, were randomized to either consume 40 g freeze-dried blueberry powder (n = 33) or placebo powder (n = 30) daily for four months. Blood draws and assessment of pain and gait were conducted at baseline, two months, and four months. Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaires were used to assess pain and GAITRite® electronic walkway was used to evaluate gait spatiotemporal parameters. WOMAC total score and sub-groups, including pain, stiffness, and difficulty to perform daily activities decreased significantly in the blueberry treatment group (p < 0.05), but improvement of WOMAC total score and difficulty to perform daily activities were not observed in the placebo group. Normal walking pace single support percentage for both limbs increased (p = or < 0.007), while double support percentage for both limbs decreased in the blueberry treatment group (p = or < 0.003). No significant changes were observed in plasma concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-13, matrix metalloproteinases (MMP)-3, MMP-13, and monocyte chemoattractant protein-1 (MCP-1) in both treatment groups. However, an increasing trend for IL-13 concentration and a decreasing trend in MCP-1 concentration were noted in the blueberry group. The findings of this study suggest that daily incorporation of whole blueberries may reduce pain, stiffness, and difficulty to perform daily activities, while improving gait performance, and would therefore improve quality of life in individuals with symptomatic knee OA.

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These data strongly suggest that maternal immune system activation plays a role in the development of pregnancy-induced hypertension (PIH).

It is necessary to eliminate linoleic acid and allergenic arachins from peanuts for good health reasons. Virginia-type peanuts, harvested from plots treated with mineral salts combinations that mimic the subunit compositions of glutamate dehydrogenase (GDH) were analyzed for fatty acid and arachin compositions by HPLC and polyacrylamide gel electrophoresis, respectively. Fatty acid desaturase and arachin encoding mRNAs were analyzed by Northern hybridization using the homologous RNAs synthesized by peanut GDH as probes. There were 70–80 % sequence similarities between the GDH-synthesized RNAs and the mRNAs encoding arachins, fatty acid desaturases, glutamate synthase, and nitrate reductase, which similarities induced permutation of the metabolic pathways at the mRNA level. Modeling of mRNAs showed there were 210, 3,150, 1,260, 2,520, and 4,200 metabolic permutations in the control, NPKS-, NS-, Pi-, NH4Cl-, and PK-treated peanuts, respectively. The mRNA cross-talks decreased the arachin to almost zero percent in the NPKS- and PK-treated peanuts, and linoleate to ∼18 % in the PK-treated peanut. The mRNA cross-talks may account for the vastly reported environmentally induced variability in the linoleate contents of peanut genotypes. These results have quantitatively unified molecular biology and metabolic pathways into one simple biotechnology for optimizing peanut quality and may encourage small-scale industry to produce arachin-free low linoleate peanuts.

Plant evolution, nutritional genomics, and mineral nutrition have been well documented but no studies have focused on the molecular adaptation of crop metabolism to wide variations of mineral ion composition and concentration. Diversification of peanut species from primary centers of domestication in South America depended on metabolic adaptation to the mineral ion conditions of the newer habitats. Understanding the diversification molecular biology of peanut metabolic pathways will permit the synthesis of the best mineral ion combinations for doubling CO₂ assimilation. Valencia and Virginia cultivars belong to different subspecies of the tetraploid Arachis hypogaea. They were planted in the absence and presence of up to 99 mM (equivalent to 166 moles per hectare) of different mineral ions. Molecular properties of the primary metabolic pathways were studied by Northern analyses using Valencia GDH-synthesized RNAs as probes for Virginia mRNA and GDH-synthesized RNAs. Messenger RNAs are silenced by homologous RNAs synthesized by GDH. Peanut cellulose was analyzed by gravimetry; and fatty acids by HPLC. Complementary DNA probes made from Valencia GDH-synthesized RNAs hybridized perfectly to Virginia mRNAs and GDH-synthesized RNAs. Wide variations in mineral ion compositions and concentrations induced the GDHs of Valencia and Virginia to synthesize RNAs that differentially down-regulated the mRNAs encoding phosphate translocator, granule-bound starch synthase, phosphoglucomutase, glucosyltransferase, acetyl CoA carboxylase, nitrate reductase, and NADH-glutamate synthase so that the percent weights of oil (41.53 ± 8.75) and cellulose (30.29 ± 3.12) were similar in the control and mineral-treated peanuts. Therefore, RNA sequences that defined the molecular adaptation of mRNAs encoding the enzymes of primary metabolism were the same in the varietal types of A. hypogaea, in agreement with genetic data suggesting that tetraploid Arachis evolved relatively recently from the wild diploid ancestral species. Another molecular adaptation was to phosphate with or without K+ ion, and it prevented the silencing by GDH-synthesized RNAs of the mRNA encoding phosphate translocator resulting to doubling of cellulosic biomass yield (41323 kg/ha) compared with the N + P + K + S-treated positive control peanut (19428 kg/ha). Molecular adaptation of primary metabolic pathways at the mRNA level to SO₄^2- ion with or without SO₄^2- ion did not increase cellulosic biomass yields (27057 kg/ha) compared with negative control peanut because the mRNAs encoding granule-bound starch synthase, and NADH-glutamate synthase were not silenced by GDH-synthesized RNA in the N + S, SO₄^2-, and N + P + K + S-treated peanuts. These results could contribute towards further modeling at the mRNA level for improved mineral nutrient management of peanut production for fuel, fiber, feed, and food

Glutamate dehydrogenase (GHD) synthesizes some RNAs that regulate mRNA abundance in response to the environment. The connection of gene expression and drug metabolism by the GDH-synthesized RNA has not been demonstrated experimentally. The regulation of the mRNAs encoding the drug-metabolizing enzymes was studied by northern hybridization using the GDH-synthesized RNAs as probes. The mRNAs encoding cytochrome P-450 reductase, UDPglucosyltransferase, alternative oxidase, and ABC-transporters were upregulated by the administered ATP+UTP+GTP. Also superoxide dismutase and GSH S-transferase were upregulated by administered ATP. The untreated control, GTP, and UTP did not upregulate any of the mRNAs. The mRNAs encoding the enzymes were coordinately regulated at the molecular level. All the enzymes are also active in drug detoxication in mammals. Photometric assays of enzyme activities confirmed that the enzymes were present at levels proportional to their respective encoding mRNAs as detected by the GDH-synthesized RNA probes. Genetic code-based nucleic acid probes were partially accurate in detecting the mRNAs encoding the enzymes. Therefore, GDH-synthesized RNAs are important genetic metabolic probes for the screening of mRNAs encoding the drug metabolizing enzymes. Nucleoside triphosphates and analogs are antihypertensives, antineoplastics, antiarrhythmics, antimetabolites, antiviral agents etc and they induce GDH isomerization.