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Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children. Although an imbalance of excitatory and inhibitory inputs has been proposed as contributing to this disorder, the mechanisms underlying this highly heterogeneous disease remain largely unknown. Here, we show that N-myc downstream-regulated gene 2 (NDRG2) deficiency is involved in the development of ADHD in both mice and humans. Ndrg2-knockout ([Ndrg2.sup.-/-]) mice exhibited ADHD-like symptoms characterized by attention deficits, hyperactivity, impulsivity, and impaired memory. Furthermore, interstitial glutamate levels and excitatory transmission were markedly increased in the brains of [Ndrg2.sup.-/-] mice due to reduced astroglial glutamate clearance. We developed an NDRG2 peptide that rescued astroglial glutamate clearance and reduced excitatory glutamate transmission in NDRG2-deficient astrocytes. Additionally, NDRG2 peptide treatment rescued ADHD-like hyperactivity in the [Ndrg2.sup.-/-] mice, while routine methylphenidate treatment had no effect on hyperactivity in these animals. Finally, children who were heterozygous for rs1998848, a SNP in NDRG2, had a higher risk of ADHD than children who were homozygous for rs1998848. Our results indicate that NDRG2 deficiency leads to ADHD phenotypes and that impaired astroglial glutamate clearance, a mechanism distinct from the well-established dopamine deficit hypothesis for ADHD, underlies the resultant behavioral abnormalities., Introduction Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder that affects 1 in 20 children and results in poor lifetime outcomes (1, 2). Males are approximately 3 to 4 times more [...]

In addition to being a component of innate immunity and an ancient defense mechanism against invading pathogens, complement activation also participates in the adaptive immune response, inflammation, hemostasis, embryogenesis, and organ repair and development. Activation of the complement system via classical, lectin, or alternative pathways generates anaphylatoxins (C3a and C5a) and membrane attack complex (C5b-9) and opsonizes targeted cells. Complement activation end products and their receptors mediate cell-cell interactions that regulate several biological functions in the extravascular tissue. Signaling of anaphylatoxin receptors or assembly of membrane attack complex promotes cell dedifferentiation, proliferation, and migration in addition to reducing apoptosis. As a result, complement activation in the tumor microenvironment enhances tumor growth and increases metastasis. In this Review, I discuss immune and nonimmune functions of complement proteins and the tumor-promoting effect of complement activation., Introduction The complement system is a cascade of serine proteases encoded by genes originating from the same ancestral genes as coagulation proteins (1). Like the coagulation system, complement activation involves [...]

BACKGROUND/OBJECTIVES: Preterm infants have low vitamin A stores at birth, and parenteral administration of high-dose vitamin A reduces pulmonary morbidity. The aim was to characterize vitamin A transport and status. SUBJECTS/METHODS: Prospective study of 69 preterm infants (median birth weight 995 g, gestational age 28 weeks), in which 51 received 5000 IU vitamin A three times per week intramuscular (i.m.) for 4 weeks and 18 infants without i.m. vitamin A served as controls. Serum retinol, retinyl palmitate, total retinol-binding protein 4 (RBP4), retinol-unbound RBP4 (apo-RBP4) and transthyretin concentrations were determined at days 3 (D3) and 28 (D28) of life. RESULTS: D3 retinol concentrations were low for the entire group (382 (285/531) nmol/l; median/interquartile range) and unrelated to gestational age. D28 retinol was unchanged in controls (382 (280/471) nmol/l), but increased in the vitamin A group (596 (480/825) nmol/l; P < 0.001). A similar pattern was observed for RBP4. The calculated retinol-to-RBP4 ratio rose in vitamin A infants (D3: 0.81 (0.57/0.94), D28: 0.98 (0.77/1.26); P < 0.01) but not in controls. In the vitamin A group, the retinol-to- RBP4 ratio was > 1 in 15% of all infants on D3 and in 45% of infants on D28, but was ≤ 1 in all, but one, controls on D28. CONCLUSIONS: In preterm infants receiving a 4-week course of high-dose i.m. vitamin A, serum retinol concentrations increased by 55%, with molar concentrations of retinol exceeding those of RBP4 in 45% of the infants suggesting transport mechanisms other than RBP4. European Journal of Clinical Nutrition (2014) 68, 1300-1304; doi: 10.1038/ejcn.2014.202; published online 15 October 2014, INTRODUCTION An adequate vitamin A supply is essential for normal fetal and postnatal development. During pregnancy, retinol reaches the fetus via the placenta, whereas after birth it is ingested as [...]

Soil-borne plant pathogens cause heavy losses to all major crops, leading to reductions in both yield and quality. Soil solarisation and bio-fumigation offer disease management options that are safe and reduce the use of pesticides for soil-borne plant pathogens. Mustard plant releases antimicrobial hydrolysis products, notably isothiocyanates when used as a bio-fumigant. Bacterial spot of tomato caused by Xanthomonas campestris pv. vesicatoria (Xcv) can survive in soil and plant debris, which serve as a primary inoculum for infecting the next tomato crop. An experiment was carried out with the objective of evaluating effects of soil solarisation and the use of Ethiopian mustard (Brassica carinata A. Braun) as a bio-fumigant to control bacterial spot disease and on yield of tomato. The treatments consisted of six types of potted soil medium (solarised at Haramaya and Dire Dawa, bio-fumigated, biofumigated as well as solarised at Haramaya and Dire Dawa, and untreated control as non-solarised non-biofumigated pots). Treated tomato seeds were planted and fruit yields were compared among treatments. Potted soil was inoculated with the pathogen, Xcv, belonging to T2P2 race group. The total microbial and Xcv counts were done before as well as after setting up the experiment. The results revealed that solarisation reduced the population of Xcv from 10.68 to 8.79 CFU [g.sup.-1], total bacterial population from 11.27 to 9.86 CFU [g.sup.-1], and total actinomycete counts from 11.69 to 9.44 CFU [g.sup.-1] while bio-fumigation had a non-significant effect on Xcv and total microbial counts. None of the treatments exhibited a significant effect on fungal counts. The fruit yield of tomato grown on biofumigated as well as solarised soil was the highest (91.18 t [ha.sup.-1]) as compared to the other treatments. It can, therefore, be concluded that solarisation and bio-fumigation cannot be used as a bio-rational option for effective management of Xcv on tomato but the two methods could be used to increase tomato yield in the presence of the pathogen. Key words: bio-fumigation, solarisation, bacterial leaf spot, INTRODUCTION Soil solarisation (SS) was introduced in 1976 with the aim of managing plant diseases [1]. The main principle of SS is to raise the temperature of a moistened soil. [...]

The origin of proteinuria is found in either the glomerular filtration device or the proximal tubular reabsorption machinery. During equilibrium, small amounts of predominantly low molecular weight proteins are filtered and reabsorbed by the receptor complex megalin/cubilin/ amnionless. This results in a protein-free filtrate passing further down the tubule. During glomerular damage, the reabsorption machinery in the proximal tubule is challenged due to elevated amounts of proteins passing the glomerular filtration slits. Even though it is considered to be a high-capacity system, several conditions result in proteinuria, thus exposing the cells in the rest of the nephron to a protein-rich environment. The impact on cells in the more distal part of the nephron is uncertain, but studies support an involvement in fibrosis development. Protein accumulation in lysosomes of the proximal tubule, due to increased protein internalization, is thought to mediate inflammation and fibrosis, eventually leading to renal failure. In contrast, low molecular weight proteinuria develops when the endocytic machinery is malfunctioning either by direct or indirect causes such as in Imerslund-Grasbeck syndrome (IGS) or Dent's disease, respectively. This review discusses the origin of proteinuria and describes the structural fundament for protein reabsorption in the proximal tubule as well as conditions resulting in low molecular weight proteinuria. Keywords Renal proximal tubule * Megalin * Cubilin * Amnionless * Endocytosis * Tubular proteinuria, Introduction Proteinuria is the presence of nonphysiological levels of a mixture of proteins in the urine (>200 mg/l). It is a characteristic of many renal diseases, and proteinuria correlates with [...]

The final step in the Kennedy pathway for seed oil synthesis is catalyzed by an acyl-CoA-dependent diacylglycerol acyltransferase, DGAT1 (EC. 2.3.1.20). We have cloned DGAT1 genes from both Arabidopsis thaliana (L.) Heynh ecotype Columbia and Brassica napus 'Jet Neuf' and over-expressed them in canola under the control of the seed-specific promoter, napin. DGAT1 from A. thaliana was inserted into B. napus 'Quantum,' whereas DGAT1 from B. napus was introduced into the B. napus double haploid breeding line DH12075. Both sets of transgenic plants exhibited increased seed oil content in both greenhouse and in field trial settings, ranging from 2.5% to 7% of dried mass on an absolute basis. The 'Quantum' transgenic lines were field-tested in plots at Watrous, Saskatchewan, in 2006 and 2007. Larger scale field trials of the DH12075 transgenics were carried out in 2007 at Ellerslie and Vegreville, Alberta. This is the first study wholly dedicated to DGAT1 over-expression and the resultant oil-content increases in transgenic canola under field conditions. Collectively, the field trial results strongly support the hypothesis that the level of DGAT1 activity during seed development in an oilseed crop can have a substantial effect on the flow of carbon into seed oil. Therefore, the overexpression of DGAT1 is a positive strategy for increasing oil content and cultivar performance in canola. Key words: cultivar improvement, Acyl-CoA:diacylglycerol acyltransferase 1, DGAT1, Arabidopsis, Brassica napus, double haploid (DH), seed oil content, field trials. L' acyltranferase du diacylglycerol acyl-CoA-dependant, DGAT1 (EC.2.3.1.20) catalyse la derniere etape du sentier de Kennedy pour la synthese des huiles seminales. Les auteurs ont clone les genes DGAT1 de l'Arabidopsis thaliana (L.) Heynh. ecotype Columbia et du Brassica napus 'Jet Neuf,' et les ont surexprimes dans le canola sous le controle du promoteur napin, specifique aux semences. Ils ont insere le DGAT1 de l'A. thaliana dans le B. napus 'Quantum,' et ont introduit le DGAT1 du B. napus dans la ligne de croisement double haploide du B. napus DH12075. Les deux ensembles de plantes transgeniques ont montre une teneur accrue en huile dans les essais en serres aussi bien qu'aux champs, allant de 2.5 a 7 % en poids sec sur une base absolue. Ils ont essaye en parcelles aux champs, les lignees transgeniques du 'Quantum,' a Watrous en Saskatchewan, en 2006 et 2007. Ils ont conduit des experiences a plus grande echelle avec les plantes transgeniques DH12075 en 2007 a Ellerslie et Vegreville en Alberta. Il s'agit de la premiere etude completement dediee a la surexpression du DGAT1 et des augmentations de la teneur en huile qui en resulte chez le canola lors d'experiences aux champs. Dans leur ensemble, les essais de terrain supportent fortement l'hypothese a l'effet que le degre d'activite du DGAT1 au cours du developpement de la graine chez une oleagineuse peut avoir des effets substantiels sur le flux de carbone vers les huiles seminales. Consequemment, la surexpression du DGAT1 constitue une strategie positive pour augmenter la teneur en huile et la performance des cultivars de canola. Mots-cles: amelioration des cultivars, Acyl-CoA:diacylglycerol acyltranferase 1, (DGAT1), Arabidopsis, Brassica napus, double haploide (HD), teneur en huile seminale, essais aux champs. [Traduit par la Redaction], Introduction Canola (Brassica napus L. and Brassica rapa L.) is a $2.5 x [10.sup.9]*[a.sup.-l] industry in Canada, with the Prairies producing the bulk of the nation's crop; more than 14.6 [...]

Author(s): Sylvie Coursol [1, 2, 3]; Liu-Min Fan [1, 2]; Hervé Le Stunff [3, 4]; Sarah Spiegel [4]; Simon Gilroy [1]; Sarah M. Assmann (corresponding author) [1] In animals, the [...]

Author(s): James E. Galagan (corresponding author) [1]; Sarah E. Calvo [1]; Katherine A. Borkovich [2]; Eric U. Selker [3]; Nick D. Read [4]; David Jaffe [1]; William FitzHugh [5]; Li-Jun [...]

Key Words neutral evolution, evolutionary rate, DNA polymorphism, Drosophila, potogene Abstract Pseudogenes have been defined as nonfunctional sequences of genomic DNA originally derived from functional genes. It is therefore assumed [...]

Objective: To assess the usefulness of the molar ratio of serum retinol-binding protein (RBP) to transthyretin (TTR) to determine vitamin A (VA) status during infection. Design: We took advantage of previously collected data during a randomised double-blind, placebo-controlled clinical trial to conduct a secondary analysis of the RBP/TTR ratio and its relationship to infection and VA status. In this clinical trial, children were randomly assigned to one of three groups and received either one single oral high dose of VA (200000 IU) on the day of admission and subsequently a placebo daily until discharge or daily oral low doses of VA (5000 IU) from admission until discharge or a placebo daily from admission until discharge. Setting: Lwiro pediatric hospital, Province of South Kivu, Democratic Republic of Congo. Subjects: A total of 900 children aged 0-72 months hospitalised consecutively between March 1994 and March 1996. Main outcome measures: RBP/TTR molar ratio after 7 days hospitalisation. Results: After 7 days hospitalisation, molar RBP:TTR ratio (mean [+ or -] s.d.) of infected children (C-reactive proteins > 10 mg/l) was 0.67 [+ or -] 0.31 in the high-dose group (n = 81), 0.74 [+ or -] 0.44 in the low dose group (n =71) and 0.73 [+ or -] 0.39 in the placebo group (n = 81). These values did not differ significantly (one-way ANOVA P=0.472). In patients with baseline serum retinol concentrations Conclusions: In this population of malnourished hospitalised children, molar RBP:TTR ratio does not appear to be useful to assess VA status during infection. Sponsorship: Our research was partially supported by a grant from the Fonds de la Recherche Scientifique et Medicale (contract 3.4505.94) and the David and Alice Van Buuren Foundation. Descriptors: vitamin A; assessment; retinol-binding protein; infection, Introduction Vitamin A (VA) deficiency remains a public health problem in more than 60 countries, especially in pre-school-age children (WHO, 1995). Worldwide, the subclinical form of the disease is predominant [...]

INTRODUCTION The ability of the immune systems of higher eukaryotes to specifically recognize and respond to most foreign proteins is generally dependent on the activation of a subclass of lymphocytes [...]

Abstract Aims--To assess changes in indicators of nutrition and iron deficiency as possible non-invasive markers of mucosal recovery in patients with coeliac disease on a gluten free diet. Methods--Concentrations of [...]

I. INTRODUCTION A great deal has occurred in the field of extracellular [Ca.sup.2+] ([[Ca.sup.2+].sub.o]) sensing since 1991 when an earlier article in Physiological Reviews addressed this subject [52]. At that [...]

Newborn children with very low birth weight may have a vitamin A deficiency. the author presents the case for this being likely. This could be critical as vitamin A is integrally involved in normal growth, differentiation of epithelial cells, and development of the urogenital system, the eyes, and the skin. The respiratory system may also be involved., ABBREVIATIONS. BPD, bronchopulmonary dysplasia; VLBW, very low birth weight; RBD, retinol-binding protein; IU, international units. Bronchopulmonary dysplasia (BPD) is the most prevalent form of chronic lung disease in infancy. Among [...]

Author(s): Neil A. Smith [1]; Surinder P. Singh [1]; Ming-Bo Wang [1]; Peter A. Stoutjesdijk [1]; Allan G. Green [1]; Peter M. Waterhouse (corresponding author) [1] Post-transcriptional gene silencing (PTGS), [...]

Abstract There is no single available measurement for evaluating the short-term response to nutrition therapy. The ideal parameter should have high sensitivity and specificity and should be unaffected by non-nutritional factors. A literature review suggested that plasma retinol-binding protein and prealbumin concentrations change earlier than albumin and transferrin levels and appear to correlate better with nitrogen balance during nutrition therapy That conclusion was supported by our own findings in patients receiving total parenteral nutrition and following the transition to oral or enteral feedings. Although concentrations of these plasma proteins have been shown to be affected by stress and renal and hepatic disease, they appear to be more sensitive indicators of the adequacy of nutrition support than other more commonly used assessment parameters. J Am Diet Assoc 89:684-687, 1989., A single indicator that would respond to nutrition therapy and correlate with adequacy of intake would be most desirable. ideally, a test to assess the response to nutrition therapy should [...]