bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular sorting studies of wild‐type and truncated forms of the D1 dopaminergic receptor unravel a chaperone‐like effect of antipsychotic drugs
Authors: Sedaghat Keyvan , Tiberi Mario 
Published: June 2021

The D1 dopaminergic receptor (D1R) is a seven‐transmembrane protein linked to stimulatory heterotrimeric GTP‐binding proteins. Here, we investigate the role of the cytoplasmic tail (CT) of D1R in regulating intracellular sorting properties of the receptor. We show that wild‐type (WT) D1R and its truncated and phosphorylation‐deficient form (Δ351) were sorted at the plasma membrane of transfected embryonic kidney 293 (HEK293) cells. Antibody feeding and co‐localization studies indicate that similar to WT, Δ351 internalizes through a clathrin‐, CT‐ and receptor phosphorylation‐independent pathway following dopamine (DA) exposure. However, in the absence of DA, Δ351 displays a strong intracellular staining unlike WT as assessed using immunofluorescence studies. Our confocal microscopy analysis shows that Δ351 co‐localizes with the endoplasmic reticulum (ER) markers, calnexin and calreticulin. Intriguingly, we observe an increase in the mature form of Δ351 and a complete rescue of ER‐retained Δ351 following an overnight treatment of transfected HEK293 cells with the inverse agonist flupentixol (Flu), an antipsychotic drug. These data strongly suggest that Flu displays a chaperone‐like effect on ER‐retained Δ351. Overall, our studies underpin a pivotal role of the CT of D1R in regulating the ontogeny and sorting to cell surface of this dopaminergic receptor subtype.Supported by CIHR (MOP‐81341; MT).
Cyclic AMP pathway and endocytic mechanisms in Trypanosomatids
Authors: Torres Héctor N. , Schoijet Alejandra C. , Docampo Roberto , Flawiá Mirtha M. , Alonso Guillermo D. 
Published: June 2021

Several species of kinetoplastids cause major human infectious diseases. Trypanosoma cruzi is responsible of the fatal Chagas disease in South America, and Trypanosoma brucei is the agent of human sleeping sickness in Sub‐Saharan Africa.In trypanosomatids, cAMP has been involved in the control of several processes such as proliferation, cell differentiation and osmoregulation. Recently, we have characterized two phosphodiesterases in T. cruzi: TcrPDEA1 and TcrPDEC2. TcrPDEC2 shows homology with PDE4 family and possess a N‐terminal FYVE domain. This domain participate in vesicular trafficking by targeting proteins containing them to membranes enriched in PI 3‐phosphate. After pre‐incubation with specific type‐4 PDE inhibitors, it was observed that parasites exposed to hypo‐osmotic stress, showed an increase in the volume recovery. Moreover, TcrPDEC2 localized close to the contractile vacuole/flagellar pocket. We also characterize a putative class III PI 3‐kinase. This enzyme, named TcVps34, is homologous to the S. cerevisiae Vps34p. By using PI3K inhibitors, it was observed that TcVps34 play a role in osmoregulation. In addition, epimastigotes over‐expressing TcVps34, showed functional and large contractile vacuoles, defects in vesicular acidification and receptor‐mediated endocytosis. Supported by CONICET, FONCYT, UBA‐Argentina and Ellison Med. Fund.‐U.S.A.
Stage‐dependent molecular changes in Notch signaling are critical for normal human T cell development
Authors: Taghon Tom , Van de Walle Inge , De Smet Greet , De Smedt Magda , Plum Jean 
Published: June 2021

Notch signaling is one of the major drivers of T cell development. While the requirements for this pathway have been well established during mouse T cell development, its role in this developmental process in human is less clear. Here, using the OP9‐DL1 coculture system, we demonstrate that different levels of Notch activation, through different downstream molecular events, are required at the major developmental checkpoints of human T cell development. We show that these Notch driven events in human induce different developmental cell fate decisions compared to during mouse T cell development. Furthermore, through characterization of the β‐selection checkpoint in human T cell development, we demonstrate that Notch signaling is mainly required for proliferation of human thymocytes, but much less important for differentiation, in contrast to during similar stages of mouse T cell development. Thus, our results reveal stage‐dependent molecular changes in Notch signaling that are critical for normal human T cell development and fundamentally different compared to the mouse.This work was supported by the Belgian Science Policy, Research Foundation Flanders (FWO), Institute for Innovation of Science and Technology (IWT) and Concerted Research Activities (GOA).
Dynamics of Tolerance induction by B‐cell delivered Gene Therapy
Authors: Matheu Melanie , Su Yan , Parker Ian , Cahalan Michael , Scott David W. 
Published: June 2021

B cells, functioning as APC's, can provide signals to T cells either activating immunity or inducing a specific hyporesponsive state (tolerance). Our laboratory has shown that B cells, when retrovirally transduced with peptide‐IgG, are highly tolerogenic for epitopes fused with the IgG. In this system, a DNA sequence encoding a full‐length protein or an immunodominant epitope is inserted into the N‐terminus of the murine IgG1 heavy chain. After injection into immunocompetent mice, peptide‐IgG transduced B cells are able to induce specific tolerance to the IgG associated antigen. This gene therapy approach has been applied to several animal models of autoimmune diseases, including EAU, EAE, and diabetes, as well as in hemophilia. In these disease models, specific tolerance was observed in both Th1 and Th2 responses. Moreover, our data indicate that the IgG heavy chain is critical for efficient tolerance induction and trafficking to endosomal processing pathways. We recently reported that activation with LPS, anti‐IgM or CD40L led to efficient tolerogenic presentation, but CpG‐activated B cells were not tolerogenic. While IL‐10 production by LPS‐activated B cells may play a role, analysis by two‐photon microscopy suggests that the LPS‐stimulated B cells interact with specific T cells longer, thus facilitating tolerogenic signals. We also propose that IgG promotes tolerance by co‐presentation of regulatory epitopes. (Supported by NIH grants AI035622 and GM41514)MM and YS contributed equally to this work
A functional polymorphism in ITPK(C) and its impact in T cell‐mediated pathogenesis of Kawasaki disease
Authors: Franco Alessandra , Shimizu Chisato , Watson Virginia , Tremoulet Adriana , Onouchi Yoshihiro , Burns Jane 
Published: June 2021

Kawasaki disease (KD) is a self‐limited, acute vasculitis that is the most common cause of acquired heart disease in children. Death by coronary artery aneurysms occurs in up to 25% of untreated children.T cells are critically involved in the pathogenesis of KD, as suggested by the infiltration of CD8+ cytotoxic T‐cells (CTL) in the coronary arterial walls of autopsy samples.Has been recently discovered a novel functional single nucleotide polymorphism (SNP) (itpkc_3) located in intron 1 in the inositol 1,4,5‐triphosphate kinase (ITPK)C gene on Chromosome 19 responsible for the reduction of the expression of the ITPKC kinase that catalyzes the phosphorylation of Ins(1,4,5)P3 to Ins(1,3,4,5)P4.We are currently studying the impact of the ITPKC locus in influencing the generation of pro‐inflammatory vs. regulatory T cells (Tregs). If we can understand the biologic effect of this SNP and its influence on disease susceptibility and outcome, this will be the first breakthrough in correlating a genotype with a phenotype in KD. Understanding this connection will have very important therapeutic implications since Cyclosporin A (CsA) specifically inhibits T cell activation affecting IL2 signaling through binding to calcineurin, which is an important downstream substrate of IP3 in the TCR‐NFAT signaling pathway.
Altered Immune Response in 2B4 Knock‐Out Mice Persistently Infected with LCMV
Authors: Waggoner Stephen N. , Mathew Porunelloor , Kumar Vinay , Welsh Raymond M. 
Published: June 2021

The signaling lymphocyte activation molecule (SLAM) family receptor, 2B4, has been implicated in regulation of lymphocyte activation in vitro and in vivo. We and others have recently observed that virus‐specific CD8 T cells display sustained, high‐level expression of 2B4 during persistent, but not acute, LCMV infection in mice. Therefore, we hypothesized that 2B4 may play a role in exhaustion of virus‐specific CD8 T cells during chronic virus infection. In contrast to the lymphopenia and T cell clonal exhaustion observed during persistent LCMV infection of wild type mice, persistently infected 2B4‐deficient mice displayed altered liver pathology and marked splenomegaly characterized by increased numbers of all lymphocytes, including CD8 T cells. There were also enhanced numbers of splenic CD8 T cells with a naïve phenotype (CD62L high, CD44 low) and a concomitant increase in the frequency of double‐positive (CD4,CD8) cells within the thymus. Lysis of LCMV peptide‐labeled CTL targets in vivo was markedly reduced in the absence of 2B4, and viral loads were elevated in the spleen and liver. We propose that the absence of 2B4‐induced regulatory signals results in reduced activation of LCMV‐specific CD8 T cells, which poorly control virus replication and resist depletion during viral infection.NIH T32 AI07349‐18
Dietary energy density among Mexican school‐age children
Authors: Moreno Lidia , Flores Mario , Macias Nayeli , Monterrubio Eric 
Published: June 2021

The goals of this study were to estimate the dietary energy density (DED) among Mexican school‐age children and to evaluate its association with dietary and socioeconomic characteristics.Data from the National Nutrition Survey 1999 of Mexico were analyzed. Dietary intake was obtained using a single 24‐hour dietary recall.DED was calculated by taking each subject's daily total energy intake in kilocalories, divided by the daily total amount of food and beverages in grams. The calculation of DED was based on systematic exclusion of different beverage categories.A total of 2,172 children 5 to 11 years age were evaluated. Fifty‐two percent were boys.As expected, the higher DED was observed when only solid foods were included (2.07 kcal/g 95%CI: 1.01, 2.03), and the lowest DED was observed when all food and beverages were included (excluding water) (1.44kcal/g, 95%CI: 1.01, 1.41).The highest DED was observed among rural children (1.54 kcal/g 95%CI: 1.48, 1.60), in children from the South region (1.56 kcal/g 95%CI:1.51, 1.62), and in children of low SES (1.60 kcal/g 95%CI: 1.54, 1.66) (p> 0.05) when all food and beverages (excluding water).A high DED was associated with poor SES conditions in Mexican school age children.Supported by the Ministry of Health, Mexico.
US Adolescent and Adult Fruit and Vegetable Intake at MyPyramid Caloric Requirement Levels among a National Sample
Authors: Kimmons Joel E , Gillespie Cathleen , Seymour Jennifer , Serdula Mary , Blanck Heidi Michels 
Published: June 2021

Background: Fruit (F) and vegetable (V) intake is associated with reduced risk for chronic disease and improved weight management.Objectives: Determine the % of adolescents and adults meeting F and V recommendations based on MyPyramid caloric requirements and identify primary contributors to overall intake.Design: 2‐day 24 hour recall data (n=5,576) was examined from the nationally representative cross‐sectional 2003–04 National Health and Nutrition Examination Survey. All dietary sources were included.Results: 0.9% of adolescents and 2.9% of adults met their caloric specific recommendations for F and V. Increased recommendations due to increased caloric requirements were not paralleled by increases in consumption. Whole F were the primary contributors to adult intake, while F juices were the primary contributor to adolescent intake. The largest contributor to F intake was orange juice. Potatoes dominated V consumption, particularly among adolescents where fried potatoes accounted for over half the median intake. Dark green and orange V and legumes account for a small portion of V intake.Conclusions: Increasing consumption of F and V will require multifaceted approaches that augment educational campaigns with policy and environmental strategies aimed at the food system. Ultimately, the goal is to increase American's consumption of F and V by making the healthy choice the easy choice.
Reconsidering child malnutrition in Mexico: A comparison of prevalences using NCHS‐1977 and WHO‐2006 growth standards
Authors: González‐Cossío Teresa , Rivera Juan A , Monterrubio Eric , González Dinorah , Unar Mishel , de Cossío Teresa González , Rivera Juan A , Monterrubio Eric , González Dinorah , Unar Mishel 
Published: June 2021

Objective: compare the prevalence of malnutrition in preschool Mexican children with the new WHO‐2006 child growth standards and with the previous NCHS‐1977 growth references.Methods: Stunting and wasting prevalences (%<−2Z height/age and weight/height respectively) with both references were estimated using data from the National Health and Nutrition Survey, a multistage stratified random sample representative at national and state levels.Results: A total of 7,802 preschool children were measured. The prevalence of stunting was 12.7 and 15.5% using NCHS‐1977 and WHO‐2006 references respectively. Those of wasting were 1.5 and 2.0%. However, the most important differences appeared in the <6mo age group, where the prevalence of wasting was 0.2 and 4.9% with the NCHS‐1977 and the WHO‐2006 references.Conclusions: Undernutrition is a greater problem in Mexico than previously estimated, particularly wasting in the very young. Breastfeeding according to WHO recommendations could prevent growth failure at this important life stage. Including breastfeeding promotion as part of the Nutrition Public Policy agenda might improve early child growth.
Dietary diversity is associated with children linear growth among poor Mexican children
Authors: Xochitl Ponce , Rodríguez Sonia , González‐Cossío Teresa 
Published: June 2021

The objective of this study was to analyze the relationship between dietary diversity and linear growth in children <5y from poor rural communities of the south of Mexico.We studied a random sample of 2469 Mexican children aged 11 to 59 months from 235 rural poor communities. Height for age Z score (HAZ) was estimated. Dietary intake was calculated from a single 24 h dietary recall. Dietary diversity (DD) was based on consumption of > 10 g of 19 different food groups. A multiple regression model adjusting for socio‐demographic co‐variables (age, sex, ethnicity, maternal education and socioeconomic status (SES)) was used to evaluate association between HAZ score and dietary diversity. Animal product consumption was significantly higher as SES improved (p<0.05), staple foods consumption such as legumes and whole cereals, was significantly higher among low SES children. DD significantly increased with age (p<0.001) and declined with SES (p<0.001). Indigenous children reported a significantly less diversified diet than non indigenous (p<0.001). DD had a positive and significant association with HAZ after adjusting for co‐variables (p<0.001). Child age, maternal education and socio‐economic status, were significantly associated with HAZ score. Ethnicity was associated with a lower HAZ score (p<0.001). Dietary diversity improves child linear growth from rural poor communities of the south of Mexico.
Increased serum leptin and decreased dental caries associated with overweight or obesity in children
Authors: Tseng Raymond J. , Wright J. Timothy , Beck Melinda A. 
Published: June 2021

Salivary and serum leptin are upregulated in overweight or obese (OWOB) adults, but this relationship is not established in young children. Salivary leptin may influence dental bacterial colonization leading to differences in incidence of caries between OWOB and lean controls (CON). The objectives were to determine if BMI, serum leptin and salivary leptin are correlated in children aged 2–7 and to determine if number of decayed and filled surfaces (DFS) in teeth differs between OWOB and CON.Children aged 2–7 were recruited, blood serum was collected and BMI was calculated. Serum leptin was quantified by radioimmunoassay. Number of teeth, and DFS were recorded after radiographic and clinical exam. Data were analyzed using ANOVA accepting p<0.05 as significant.Serum leptin was significantly elevated in OWOB versus CON and correlated with BMI. CON and OWOB females produced more leptin than males. Salivary leptin was not detectable via conventional RIA in this population. Total number of teeth did not significantly differ between OWOB and CON. OWOB had significantly fewer decayed teeth, and fewer anterior DFS.Children as young as 2 exhibit elevated serum leptin levels. Females are more prone to this effect than males. Salivary leptin is not detectable by conventional methods in this population. OWOB children had significantly less dental decay.
Comparison and precision of the XCT 3000 and XCT 2000 peripheral quantitative computer tomography densitometers for geometric and material bone parameters of the radius
Authors: Koenig Cory , Binkley Teresa , Specker Bonny 
Published: June 2021

Use of peripheral quantitative computed tomography (pQCT) in research has increased in the past decade. This study compares bone measures from two pQCT densitometers: the XCT3000 and the XCT2000 (Orthometrix Inc., White Plains, NY). Coefficients of variation (CV) for the XCT3000 also are reported.Images from the distal radius (4% site) and radial shaft (20% site) in 35 (19 male) healthy individuals were obtained using the XCT2000 and XCT3000. Age ranged from 13–75 years (mean 32 years). Mean height was 172.7±11.3 cm and weight was 77.0±20.6 kg. CVs for the XCT3000 were calculated from duplicate scans and ranged from 1.3% for total bone content to 7.5% for trabecular bone content (4% site) and from 0.7% for cortical volumetric bone mineral density to 2.7% for endosteal circumference (20% site). There were no differences in the means of any of the bone measures between the two machines. Strong associations between the XCT2000 and XCT3000 measures were noted (R‐value ranging from 0.92 to 1.0). Trabecular density and total bone content (4% site) had mean differences (XCT3000‐XCT2000) not equal to zero, other bone measure mean differences were not different from zero. Adjustments between the machines may need to be made for trabecular density and total bone content at the 4% site.Supported by: EA Martin Program in Human Nutrition at South Dakota State University.
Fiber and experimental carcinogenesis
Authors: Pereira Paula Cardoso , Cabrita Antonio Silvério , Silva Teresa Simões , Mesquita Maria Fernanda , Saldanha Helena 
Published: June 2021

Mechanisms by witch fiber could exert its protective effects include changes of metabolism of estrogens, resulting in less estrogen bioavailability, and the introduction of phytoestrogens and some antinutrients like protease inhibitors that can remove fatty acids, carbohydrates and other nutrients, thereby reducing their absorption. This study intended to establish the relation between two types of diets with different energetic value and fiber content in the number, volume of breast cancer tumours.Two groups of Sprague‐Dawley rats (n=48; 50 days) were divided and housed 4 in each plastic cage in a holding room under constant conditions of 22o±2oC, 55±10% humidity and a 12 h light/dark cycle. In all animals were administrated 20 mg of DMBA in olive oil, by gavages, had free access to water and food. Diets consisted in a richer fiber food with 250 Kcal/100g (Group I) and the same diet supplemented with beans (40 g of lyophilized beans/Kg) and olive oil (50 ml/Kg) in group II. Sacrifice ended in 150 days. Weight gain was monitored every two weeks. A blood sample was collected before administration of DMBA and in sacrifice. A non‐significant variation was observed in biochemical parameters however a high significant difference (p<0,0001) was observed for mammary tumours number and in weight gain. These results suggest that a rich fiber diet may prevent mammary carcinogenesis.
Effects of maternal dietary intake on blood heavy metal levels in antepartum and postpartum
Authors: Lee Ah Young , Kim Hyesook , Chang Namsoo 
Published: June 2021

Although adequate dietary intake of maternal is supposed to have beneficial effects on development of infants, it may be harmful for child growth and development since specific food is a common source of heavy metal. The purpose of the present study was to investigate antepartum and postpartum blood mercury, lead and cadmium levels in relation to maternal food intake. Among 422 pregnant women (18–20 wk), whose dietary intake during pregnancy was assessed by a 24‐hour recall method, maternal blood heavy metal levels were analyzed by atomic‐absorption spectrometry methods. Maternal whose intake of meats and vegetables were above the median value showed high in antepartum blood lead level than those with intakes below the median. Maternal whose intake of beans was above the median value showed high in antepartum blood cadmium level than those with intakes below the median. Antepartum blood lead level of maternal was positively correlated with meat and meat products intake during pregnancy. Postpartum blood mercury level was positively correlated with mushrooms and beverages intake during pregnancy. Postpartum blood cadmium level was positively correlated with seaweeds intake during pregnancy. These results suggest that food intake during pregnancy may effects antepartum and postpartum blood mercury, lead and cadmium levels of maternal.This work was supported by the Ministry of Environment and the Brain Korea 21 project in 2007.
Fermented Soy Product Reduces Adipose Mass, Improves Insulin Sensitivity and Alters Adipose Tissue Gene Products in Mice
Authors: Shrode Gayle E. , Cole Rachel M. , Koba Kazunori , Tanimoto Hiroyuki , Okabe Yuki , Belury Martha A. 
Published: June 2021

Obesity is a problem affecting much of the world. Intake of soy may decrease tissue lipid accumulation and adipose tissue mass. We aimed to determine the effect of fermented soy product on weight gain and adiposity in growing male C57Bl/6 mice. Eight week old mice were put in a Casein Diet (C), Soy Diet (S), or Fermented Soy Diet (F) group for 17 weeks. Half of the mice fed C were switched to F at 8 weeks (CtoF). F reduced weight gain and adiposity compared to S and C. At 16 weeks, fasting glucose from the F was significantly lower from the C or S. In an insulin tolerance test (ITT), glucose lowering was more dramatic from F compared to S or C. Fasting insulin was significantly lower from F and S verses C, and the F group was significantly lower than the S group. Serum leptin was significantly reduced from F and S compared to C. mRNA of adiponectin and adipose triglyceride lipase (ATGL) were significantly elevated from S compared to C while F had no effect. F significantly lowered levels of peroxisome proliferator activated receptor gamma (PPARγ) compared to S. F reduced adipose mass, plasma insulin and glucose, serum leptin, and adipose tissue responses in fatty acid‐binding protein‐4 (FABP‐4), PPARγ, hormone‐sensitive lipase (HSL) and ATGL gene transcription. Protein analysis of PPAR responsive genes and histological evaluation will provide further insight to the mechanism.This work was supported by Ajinomoto Corp.