bluuebunny/crossref_metadata_2025_split huggingface dataset:
TTP4000, a soluble fusion protein inhibitor of Receptor for Advanced Glycation End Products (RAGE) is an effective therapy in animal models of Alzheimer's disease
Authors: Zhou Bin , Rothlein Robert , Shen Jane , Valcarce Carmen , Selmer Johan , Hanhan Marwan , Kindy Mark S , Mjalli Adnan M.M. , Kostura Matthew J 
Published: June 2021

RAGE is a member of the Ig supergene family that binds with nanomolar affinity to amyloid beta (Aβ) peptides which are implicated in the pathology of neurodegenerative Alzheimer's disease. RAGE expression is upregulated in Alzheimer's brains and involved in the retention of Aβ in the brain and inflammation in the neurovascular unit. Double transgenic mice that over‐express human RAGE and human amyloid precursor protein (APP) with the Swedish and London mutations in neurons develop learning defects and neuropathological abnormalities earlier than their mutant hAPP transgenic counterparts. Double transgenic mice expressing a dominant negative form of RAGE on the same mutant hAPP background, show a delayed onset of neuropathological and learning abnormalities compared to the APP transgenic background counterpart. This data suggests that interfering with RAGE signaling may have benefit in Alzheimer's disease.To test the therapeutic benefits of inhibition RAGE signaling. We have developed a novel fusion protein, TTP4000, using the binding domains of sRAGE linked to a human Ig Fc domain. TTP4000 has similar binding characteristics to ligand as sRAGE but a superior pharmacokinetic profile. We have tested TTP4000 in a mouse model of Alzheimer's disease and show that the protein is well tolerated and efficacious. TTP4000 was shown to significantly reduce soluble Aβ levels in brains of mice. The reduction of soluble brain Aβ levels correlated with a decrease in plaque load, a reduction in inflammatory cytokine levels and improved measures of behavior in the Morris Water Maze test. These data confirm and extend previous reports implicating RAGE in the pathogenesis of Alzheimer's disease and indicate that TTP4000, an injectable RAGE antagonist, is a viable treatment for Alzheimer's disease.
CTBP regulates the early SEC assembly prior to onset of transcription elongation
Authors: Byun Jung S , Gardner Kevin 
Published: June 2021

The C‐terminal binding proteins (CtBP1 and CtBP2) are a dimeric family of proteins encoded by two genes, CtBP1 and CtBP2 that play various roles in cell differentiation, wound healing and EMT. One member of the dimer functions to bind numerous chromatin sequence‐specific transcription factors, while the other member recruits several different chromatin modifying complexes. In this way, CtBP has a broad potential to influence the epigenetic landscape of the nucleus. CtBP shares many amino acid homology with NADH‐dependent 2 hydroxyacid dehydrogenase and previous report suggested that CtBP has a ~ 100 fold higher nanomolar affinity for NADH than NAD+ and nuclear NADH induces conformational change in CtBP. It has been known that CtBP1 physically associates with the bromodomain of histone acetyltransferase of p300 and regulates the direct interaction between the bromodomain of p300 and acetylated histones in an NADH‐dependent manner.We found CtBP forms complexes with p300 in resting cells of HEK293ET and CtBP depletion increases early elongation complex assembly and early mRNA transcription. We also showed CtBP overexpress repressed immediate early gene expression by attenuating early elongation and CtBP depletion increased the duration of immediate early transcription.
Cognitive impacts of diet quality depend on socioeconomic position: the NuAge study
Authors: Parrott Matthew , Shatenstein B , Ferland G , Morais JA , Belleville S , Kergoat MJ , Payette H , Greenwood CE 
Published: June 2021

We examined whether equivalent adherence to ‘Prudent’ and ‘Western’ dietary patterns, identified by principle components analysis, exerted the same beneficial or detrimental effects on cognitive function (Modified Mini‐Mental State Examination; 3MS) in older adults with different socioeconomic position (SEP). The interaction of dietary pattern adherence with household income, educational attainment, occupational prestige, and a composite indicator of SEP combining all three (n=1099) was examined in multiple‐adjusted mixed models over 3 years of follow‐up. Adherence to the Prudent pattern was related to higher 3MS scores at recruitment only in upper categories of income (P=0.015), education (P=0.017), or composite SEP (P=0.026). High Prudent pattern adherence was associated with slower cognitive decline only in those with low composite SEP (P=0.042). Conversely, high Western pattern adherence was associated with accelerated cognitive decline (P=0.023) only in those with low educational attainment. In summary, we found that the neuropsychological parameters of the diet‐cognition relationship were dependent on SEP. Since individuals with equivalent diet quality and dissimilar SEP performed differently, it may be unrealistic to expect diet to act on cognition in isolation from other dimensions of lifestyle.Grant Funding Source: Canadian Institutes of Health Research
Food consumption in the Nigerian population: Estimates of energy and micronutrient intakes and main food sources of energy, iron and zinc
Authors: Bermudez Odilia I. , Lividini Keith , Fuster Melissa , Smitz Marc‐ Francois , Fiedler John L. 
Published: June 2021

ObjectiveTo estimate baseline intakes and food sources of energy (E), and the micronutrients (MN) iron (Fe) and Zinc (Zn) for the Nigerian population.MethodsFood sources and apparent intakes of Fe & Zn were estimated with food acquisition data from the 2003–04 Nigeria Living Conditions Monitoring Survey. Applying adult male equivalents (AME), individual intakes and levels of inadequacy were assessed. Intakes of MN were adjusted by bioavailability. All estimates were adjusted with sample weights.ResultsMain sources of E were corn (20%), rice (17%), gari (11%) and pulses & nuts (P&N, 11%). P&N, corn and rice provided 25%, 21% & 8% of Fe plus 21%, 27% and 15% of Zn, respectively. National intake of energy was 1,290 Kcal/AME, while MN intakes were 10.6 mg for Fe and 6.4 mg for Zn, per AME. Dietary recommendations (EARs) for Fe and Zn reached, as mean, 54% and 87% of the EAR, although the median EARs were only 37% and 52%. The population at risk of inadequate intakes was 70% for Fe and 76% for Zn.ConclusionsWe were able to obtain estimates of baseline apparent food intakes using food acquisition data from a national survey from Nigeria, from which we identified elevated proportion of the Nigerian population at risk of inadequate intakes of Fe and Zn.Funding:Bill & Melinda Gates Foundation Grand Challenge Grant
VO2 max improves in Indian school children after a feeding trail with iron biofortified pearl millet
Authors: Pompano Laura M. , Przybyszewski Eric M. , Udipi Shobha A. , Ghugre Padmini , Haas Jere D. 
Published: June 2021

ObjectiveTo examine the effects of an iron biofortified pearl millet intervention on physical performance in children, measured by VO2max.Methods135 children (11–18 y) were enrolled in a randomized trial of an iron biofortified pearl millet intervention (vs. control pearl millet), daily for a 6 month period in India. VO2max at baseline and end line was calculated from oxygen consumption and heart rate during a sub‐maximal exercise test on a cycle ergometer. General linear models were used to evaluate the effect of the intervention on VO2max in children.ResultsAt baseline 32% of subjects were iron deficient with serum transferrin receptor (sTfR) values above 8.0 mg/L. The average VO2max at baseline was 36.9 mL/kg/min for girls. After six months, there was a significant relationship between decreasing sTfR (improved iron status) and increased VO2max in the iron biofortified pearl millet group, but not in control group (P<0.01 and P=0.10, respectively).ConclusionsSupplementation with iron biofortified pearl millet significantly improved VO2max in children.Grant Funding Source: HarvestPlus
Consumption of flavored waters, sports and energy drinks is potentially underestimated: trends in sales, purchases and intake in the US, 2000–11
Authors: Stern Dalia , Piernas Carmen , Popkin Barry M 
Published: June 2021

New caloric beverage options are increasingly being introduced. We investigated the dynamics of consumption of flavored waters (FW), sports (SD) and energy drinks (ED) in the US.We analyzed per capita volume (mL/day) of FW, SD and ED using three sources of data for the US population: NHANES 2003–10 dietary intake data; sales data from Euromonitor (EM) 2000–11; purchases from the Homescan Longitudinal (HM) dataset 2000–11. This analysis was restricted to consumer‐packaged goods from convenience/grocery stores, excluding vending and away‐fromhome sources. Trends for each beverage group were explored in sales (EM 2000–10) and intake (NHANES 2003–10). Total intake (NHANES) with total purchases (HM) for 2007–08 (later all 11y) were examined. Survey commands were used to account for survey design (STATA 12).SD ranked the highest among intake, sales and purchasing data, followed by FW and ED. Overall, we found increasing trends in sales (EM) of SD, FW and ED whereas trends in intake (NHANES) declined for these beverage groups. In addition, the absolute per capita volume (mL/day) of sales (EM) was significantly higher compared to intake (NHANES). Purchase and intake patterns are comparable.These different trends and intake levels between commercial data and NHANES reported intake suggest potential underreporting of these new beverages, which represent important new sources of added sugars in the US diets.Grant Funding Source: Robert Wood Johnson Foundation Grant 70017; National Institutes of Health R01‐HD030880 R01‐ HL104580 R01‐HL114091 R01‐HL108427; Conacyt Grant 309902
Does thawing and warming affect the integrity of human milk?
Authors: Handa Deepali , Ahrabi Ali Faraghi , Codipilly Champa N , Shah Syed , Potak Debra , Schanler Richard J 
Published: June 2021

ObjectiveAs most neonates in the NICU are fed defrosted human milk (HM), we evaluated the integrity of the HM after freezer storage, thawing, warming, and waiting to be fed.MethodsNICU mothers (n=41) donated 100 ml of milk. Baseline aliquot was stored at −80°C, and the remaining milk was stored 7 days at −20°C. Subsequently, milk was thawed and warmed using tepid water or waterless warmer. A separate sample of thawed milk was maintained in refrigerator for 24 h and warmed. Warmed milk was maintained at room temperature (RT) for 4 h. Milk integrity was described as the effect on pH, protein, sIgA, lactoferrin, and bacterial colony counts (total, TBCC; Gram positive, GPCC; Gram negative, GNCC). Data analyzed by ANOVA and paired t test.ResultsThere were no differences in milk integrity between the two warming methods. There were no changes in protein, sIgA, and lactoferrin with processing. There was a significant change in pH between baseline, thawing, and warming, p < 0.001. When thawed milk was warmed after refrigeration, there was a further decline in pH. TBCC, GPCC, GNCC did not change significantly with processing but when warmed milk was maintained at RT all counts increased, p < 0.01.ConclusionThawing and warming do not change the integrity of previously frozen human milk adversely. The integrity of the milk is affected similarly by the two methods. Concerns about maintaining warmed milk at RT need to be explored.
EFFECTS OF DIFFERENT CALORIE RESTRICTION DIETS IN OBESE WOMEN
Authors: de Toledo Triffoni‐Melo Andresa , Jordão Alceu Afonso , Dick‐de‐Paula Ingrid , Ovídio Paula Payão , Diez‐Garcia Rosa Wanda 
Published: June 2021

The aim of this study was to compare the short‐term effects of two different calorie restriction (CR) diets on anthropometric and biochemical parameters in obese women. Participants were 30 women, BMI 37.3±4.4kg/m2, and 39±6.3 years of age. This study was conducted in 3 phases with a follow‐up at one month from the end of phase 3. In Phases 1 and 3 participants were on an ad libitum diet at home for 2 days. In Phase 2, participants were on a 1000 kcal/d CR diet for 3 days and were randomized to either the experimental group (EG n=15), which received a high‐fiber diet or the control group (CG n=15), which received the conventional diet. Anthropometric and biochemical data were collected at the beginning and end of each phase for a total of 5 measurements including the 1month follow up period. There was no significant reduction within groups in body weight (EG, p=0.92; CG, p=0.95) and waist circumference (WC: EG, p=0.97; CG, p=0.98). No significant between groups difference in weight (p=0.92) or WC (p=0.85) were observed. A significant reduction in fasting glucose (p=0.01) was observed within the EG during CR. There was also a reduction of triglycerides (p=0.03) in EG compared to CG. The results of this short‐term study indicate that a high‐fiber diet results in a greater decrease in fasting glucose and triglycerides, compared to a conventional diet.This research was supported by The State of São Paulo Foundation (FAPESP).
Interactions between physical performance, body‐composition and nutrition in individuals one to three years after stroke
Authors: Vahlberg Birgit Maria , Lindmark Birgitta , Zetterberg Lena , Hellström Karin , Cederholm Tommy 
Published: June 2021

Interactions between physical performance, body composition and nutrition in individuals 1–3 years after stroke.ObjectiveTo explore muscle mass, physical activity and nutritional status and association to mobility in stroke survivors.Methods134 community living individuals (74±5 y, 69% men) participated. Mobility was measured by Short Physical Performance Battery (SPPB, 0–12 points). Bio‐impedance analysis (BIA) measured fat free mass index (FFMI; kg/m2), fat mass index (FMI; kg/m2) and FM%. Nutritional status was measured by Mini Nutritional Assessment‐Short Form (0–14 p), gait speed by 10 m walking test (m/s) and the self‐reported Physical Activity Scale for the Elderly (PASE, ≥0 points) were recorded.ResultsBMI showed that 71% were overweight or obese. 14% were at risk for malnutrition. FM% was >;20 in 86% of men, and >;30 in 90% of women (related to a ref population). 28% were considered as sarcopenic obese, i.e. FFMI <25th perc + FMI>;50th perc of a ref population. Sarcopenia, i.e. the combination of FFMI<25th perc of normal + gait speed <1 m/s, was observed in 10%. Walking speed was slow (1.1±0.25 m/s), and PASE was low (mean 108±65 p). SPPB was reduced (median 10 p), but neither associated to FFMI nor FMI. Logistic regression indicated that SPPB ≤9 p was significantly related to risk for malnutrition; OR 5.8, reduced physical activity; OR 8.2, and high age; OR 2.8 for each 10 y.ConclusionsObesity was observed in ~2/3 subjects 1–3 y after stroke. More than 1/4 was classified as sarcopenic obese. FFM was not related to physical performance, whereas risk for malnutrition, physical activity and age were. Thus, nutrition and physical activity may represent opportunities for rehabilitation after stroke.
The effects of high fiber noodle on metabolic syndrome
Authors: Chiang Pei‐Chin , Yang Ji‐Hua , Chen Pei‐Tung , Chiu Wan‐Chun , Chien Yi‐Wen 
Published: June 2021

In view of metabolic syndrome is a global health issue, the aim of the study was to investigate the effect of high fiber noodle (HFN) and fibersol‐2 on its major indicators ‐ hyperlipidemic and diabetic animals. In hyperlipidemic model, male Syrian Hamsters were divided into 4 groups and fed a high fat with 0.2% cholesterol‐enriched diet. Animals were fed the diet without HFN (C) or with 1.2% fibersol‐2 and 14.8% HFN (1x), with 2.4% fibersol‐2 and 13.6% HFN (2x), with 6% fibersol‐2 and 10% HFN (5x), respectively. In diabetic model, male Wistar rats were divided into 5 groups and fed AIN‐93M diet, and 4 groups of rats were induced diabetes by streptozotocin. Normal rats were fed the diet without HFN (N), and diabetic rats were fed AIN‐93M with C, 1×, 2×, 5× diet, respectively. After 8 weeks, we analyzed blood lipids and glycemic parameters to determine whether HFN can reduce the lipid and glucose levels. The results in hamsters showed serum total cholesterol level and low‐density lipoprotein cholesterol, 1×, 2× and 5× were all lower than those in C group (p<0.05). Otherwise, the results in rats showed fasting plasma glucose and area under the blood glucose curve, 5× was lower than C group (p<0.05). In summary, the study demonstrated that intake HFN with fibersol‐2 can regulate blood lipids, fasting blood glucose and postprandial blood glucose to improve metabolic syndrome.Grant Funding Source: Taipei Medical University
Eicosapentaenoic acid prevents high fat diet‐induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanisms
Authors: LeMieux Monique , Kalupahana Nishan , Xin Wenting , Thanamool Catthareeya , Voorhees Victor , Siriwardhana Nalin , Claycombe Kate , Moustaid‐Moussa Naima 
Published: June 2021

Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high‐fat (HF) diet‐induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for these effects. Gene (microarrays and RT‐PCR) and protein expression studies (immunoassays) revealed changes in levels of genes/proteins associated with cell proliferation, apoptosis, adipocyte differentiation and glucose metabolism. Specifically, expression of lipogenic/adipogenic markers (Fasn, Srebf1, Cebpa, Ncoa2, Wnt signaling) were decreased by EPA. Metabolomic analyses confirmed enrichment of adipose tissue in n‐3 polyunsaturated fatty acids (PUFAs) and a decrease in n‐6 PUFAs in both visceral and subcutaneous fat. These studies also indicated increased oxidation of stored fatty acid and increased fatty acid oxidation related‐metabolites such as acetylcarnitine. Together the genomic and metabolomic findings were in‐line with other metabolic and physiologic outcomes including decreased adiposity and fat cell size and increased lipid oxidation. In conclusion, our studies demonstrate that EPA ameliorates glucose homeostasis at least in part by reducing adipose tissue inflammation and lipid accumulation and increasing fatty acid oxidation.Grant Funding Source: UT AgResearch and College of Human Sciences / Texas Tech University
The non‐neuronal cholinergic system: sources of vascular ACh
Authors: Davis Harrison , Smith Kirsty , Bagher Pooneh , Dora Kim , Garland Christopher 
Published: June 2021

The localisation of muscarinic receptors in vascular endothelial cells and the consequences of activation of these receptors are extensively documented. However, it is not known if endogenous acetylcholine is available to activate receptors, and if so where it originates. As acetylcholine (ACh), its receptors and synthesising enzymes are widely expressed in extra‐neuronal cells and tissues (the non‐neuronal cholinergic system) including blood cells, we investigated a potential role for these cells as a source of endogenous ACh to stimulate the endothelium. Isolated rat mesenteric arteries were cut open and fixed en‐face. Endothelial cells were loaded with a calcium dye to measure levels of intracellular calcium using confocal microscopy. Endothelial cells exhibited transient but pronounced calcium increases when exposed to rat whole blood. The frequency of endothelial cell calcium events, average fluorescence and the number of active cells increased significantly above the spontaneous basal activity. ATP was shown not to be a component of this response, however, a trend in sensitivity to block with atropine (1μM) was observed. Taken together these data suggest that ACh may originate in sufficient quantities from blood cells to stimulate endothelial cell calcium increases. As such this may represent a significant auto or paracrine influence on vascular tone.Work funded by the British Heart Foundation.
Identifying key residues important for CGRP binding to its receptor
Authors: Kuteyi Gabriel , Barwell James , Poyner David 
Published: June 2021

The calcitonin gene‐related peptide (CGRP) is a 37 amino acid neuropeptide. Its receptor is a heterodimeric complex of calcitonin receptor‐like receptor (CLR) – a family B G‐protein coupled receptor – and a single‐pass transmembrane protein, receptor activity modifying protein 1 (RAMP1). Here, we identify residues, within the N‐terminal extracellular domain (ECD) of CLR, potentially involved in ligand binding.Certain residues presumed to be possible sites of contact for the CGRP were picked from the CLR/RAMP1 ECD crystal structure (PDB 3N7S). Residues were mutated to alanine (A) by site‐directed mutagenesis (QuikChange™, Stratagene). Mutants were transiently co‐transfected with HA‐tagged CLR and RAMP1into COS7 cells using PEI. After 48 hr, cells were treated with 10pM – 100nM CGRP for 15 min. cAMP production was assessed by a radio‐receptor assay. Concentration‐response curves were analysed with Graphpad Prism 4.00 to give pEC50 values. Cell surface expression was determined by enzyme‐linked immunosorbent assay (ELISA) (Barwell et al., 2011).All mutants (Table 1) showed reduced potency, though to varying degrees. W69A and D70A showed significant reduction in cell surface expressionThese findings suggest that these residues are important for the interaction of CGRP with its receptor. W69A and D70A, part of the WDG motif of family B GPCRs, are thought to rather play a role in receptor stability (Kumar et al., 2012). The data is consistent with CGRP binding in a groove between CLR and RAMP1.This project was supported by Aston School of Life and Health Sciences
Modulation of sirtuins during acute inflammatory pain: the role of ROS
Authors: Muscoli Carolina , Lauro Filomena , Ilari Sara , Pucci Bruna , Dagostino Concetta , Gliozzi Micaela , Tafani Marco , Palma Ernesto , Ventrice Domenica , Russo Matteo , Fini Massimo , Mollace Vincenzo , Salvemini Daniela 
Published: June 2021

Free radicals plays a crucial role in the enhanced pain sensitivity experienced during inflammatory diseases. ROS accumulation modifies the activity of sirtuins (SIRT 1–7), proteins that deacetylate histones and non‐histone proteins playing an important role in regulation of inflammation and neurodegenerative diseases. SIRT1 either directly or indirectly influences the redox property of the cell and it is also regulated by oxidative stress. SIRT3 plays a role in the maintenance of basal levels of reactive oxygen species; it stimulates MnSOD and catalase production by FOXO activation as SIRT1 and deacetylates two critical lysine residues on MnSOD itself to promote its antioxidative activity. We show that removal of free radicals by antioxidants is able to block the thermal hyperalgia in the carrageenan‐induced inflammation model. This effect was associated with inhibition of edema, lipid peroxidation, nitrotyrosine formation and PARP activation in the paw exudates and to nitrotyrosine formation in the spinal cord. We report that SIRT1 and SIRT3 are decreased in the spinal cord of carrageenan treated rats and that removal of free radicals by antioxidant enhanced their expression. These findings demonstrate for the first time that sirtuins activation by antioxidants is beneficial during oxidative stress induced hyperalgesia and inflammation.This work has been supported by PON a3–00359 and GR‐2010–2318370