bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphatidylinositol (4,5)‐bisphosphate regulates psychostimulant behaviors through its interaction with the dopamine transporter (803.2)
Authors: Hamilton Peter , Belovich Andrea , Khelashvili George , Saunders Christine , Erreger Kevin , Javitch Jonathan , Sitte Harald , Weinstein Harel , Matthies Heinrich , Galli Aurelio 
Published: June 2021

Phosphatidylinositol (4,5)‐bisphosphate (PIP2) is known to regulate the function of ion channels and transporters. The human dopamine (DA) transporter (hDAT) is a key regulator of DA homeostasis and a target of the psychostimulant amphetamine (AMPH). AMPH’s addictive properties are mediated, at least in part, through elevation of extracellular DA by inducing DA efflux through the DAT. Thus, the objective of our study is to understand how to precisely manipulate the DAT to prevent DA efflux without altering its physiological function of DA uptake. This understanding is paramount to the development of pharmacological therapies for AMPH abuse. Here, we demonstrate that PIP2 directly binds to the hDAT. This binding occurs through electrostatic interactions with positively charged hDAT N‐terminal residues and is shown to facilitate AMPH‐induced, DAT‐mediated DA efflux and the psychomotor properties of AMPH. Substitution of these residues with uncharged amino acids reduces hDAT‐PIP2 interactions and AMPH‐induced DA efflux, without altering the hDAT physiological function of DA uptake. We evaluated, for the first time, the significance of this interaction in vivo using locomotion as a behavioral assay in Drosophila melanogaster. Expression of mutated hDAT with reduced PIP2 interaction in Drosophila DA neurons impairs AMPH‐induced locomotion without altering basal locomotion. We present the first demonstration of how PIP2 interactions with a membrane protein can regulate organismal behaviors, such as locomotion.Grant Funding Source: Supported by DGE0909667 & F31 DA 035535‐01(PJH), P22893(HHS), DA13975(AG), P01 DA12408(AG, HW, JAJ)
Food security and access to water in Mexican households (805.1)
Authors: Monroy‐Torres Rebeca , Naves‐ Sánchez Jaime , Melgar‐Quiñonez Hugo 
Published: June 2021

Introduction: Food security is the state in which all persons always have access to the food needed according their biological requirements, but since 2002, the FAO has mentioned that food security cannot be achieved without considering the access to water. Objective: To identify the state of food security and access to water in Mexican households. Methods: Food Security was assessed using a validated scale applied in 352 households in rural and urban communities, as well as a pilot scale to assess access to water. Results: 73 % of households were classified as food secure (level 1), 15 % as being mildly food insecure (level 2), 7% were considered food insecure at a moderate level (level 3) and only 4 % were households with severe food insecurity (level 4). At all food security levels interviewees were worried about not having enough access to water, and in the last three months 50% of households experiences water scarcity. Most of the households used tap water to prepare the milk for the children, as well as for personal hygiene. 25% of the interviews reported that water availability has declined in their households, while the cost of water has increased. Conclusions: Food security cannot be conceived without taking into account the water situation. The majority of the households report lack of access to enough water, which usually does not meet the conditions of safety for human consumption and food preparation.Grant Funding Source: None funding
Serving vegetables in multiple locations in school lunchrooms can lead to increased vegetable selection (808.10)
Authors: Hanks Andrew , Just David , Wansink Brian 
Published: June 2021

Objective: To determine the impact on selection and consumption of fruits and vegetables in school cafeterias when fruits and vegetables are served both on the hot lunch line and in a separate location, such as a salad bar.Methods: Twenty‐five schools of all age levels agreed to participate in the study. Of these schools, 5 served fruits and vegetables both on the hot lunch line. Three of these schools were elementary schools, and two were middle schools. Fruit and vegetable selection and consumption data were collected on four different days in all the schools. Standard t‐tests were used to compare differences in fruit and vegetable selection and consumption.Results: In cafeterias where fruits and vegetables were served in two separate locations, students took 20% more hot vegetables (p=0.015) and 41% more cold vegetables (p<0.001), such as salad. Fresh fruit selection, on the other hand, decreased by 9% (p=0.023).Conclusions: More is not always better. In school lunchrooms, serving vegetables in more than one location tends to increase the number of servings of vegetables, both hot and cold, that students take. Yet, when fruits are served in two locations, students take fewer servings of fresh fruits, possibly because they gravitate towards vegetables. Yet, there are methods available for gently nudging students to take more of the healthy items they are offered, regardless of the number of locations in which they are served.
Dietary behaviors are rapidly changing in China, 1991 ‐ 2011 (811.24)
Authors: Du Shufa , Du Wenwen , Zhang Bing , Wang Huijun , Popkin Barry 
Published: June 2021

In low and middle income countries, few studies on away‐from‐home consumption exist. Our study examines the patterns and trends using China Health and Nutrition Survey data (1991– 2011) for 32,024 individuals aged 2 years old and older. Detailed dietary data was collected by three consecutive 24–hour recalls with weighing of all foods and condiments. Meal preparation locations were categorized into home, restaurants, work/school cafeteria, and their combinations. Random effects regression models were used to examine the patterns and trends. Over the 20 years of study period, age‐standardized energy from food prepared at home significantly decreased, while restaurant food increased from 6.6% to 15.9%, from 7.9% to 21.9%, and from 8.6% to 15.0% among participants aged 2‐18 years, 19‐59 years, and 蠅60 years, respectively. About 50.0% of energy was from away‐from‐home‐eating in 3 autonomous mega cities (Beijing, Shanghai, and Chongqing) in 2011. Modernization (both urban and rural areas measured by an urbanicity index) and increased income are driving these dietary patterns shifts. China is rapidly shifting away from home‐cooking rapidly, although overall energy intake from away‐from‐home‐eating remains lower than that in higher income countries.This study was supported by the NIH (R01‐HD30880) and the Fogarty International Center, NIH (5D43TW007709).Grant Funding Source: NIH
Alternative transcripts in the human milk fat globule proteinogenic RNA transcriptome with emphasis on desaturases (818.8)
Authors: Kothapalli Kumar , Guo Xiaoxian , Sun Xuepeng , Hyon Stephanie , Ran‐Ressler Rinat , Zou James , Gu Zhenglong , Brenna James Thomas 
Published: June 2021

Introduction. Human breastmilk carry fat mostly in milk fat globules (MFG). Our aim was to investigate proteinogenic RNA with emphasis on PUFA synthesis in MFG.Methods. Fresh human breastmilk sample from a single donor was centrifuged and MFG collected for mRNA isolation. An Illumina HiSeq implementing RNASeq detected >15,000 transcripts.Results. The most highly expressed transcripts were associated with protein translation and elongation, milk protein, MFG formation, fatty acid metabolic process and transport, iron ion transport, regulation of apoptosis, and cellular component size. Six transcripts (CSN2, LALBA, CSN3, FTH1, CSN1S1 and CSN1S2AP) accounted for the bulk of the MFG transcriptome. Alternative splice sites were identified for >3500 genes in MFG. A novel FADS2 alternative transcript (FADS2AT2) with 386 amino acids was detected. FADS2, FADS2AT1 and 5 out of 8 known FADS3AT were expressed in MFG; FADS1, FADS3AT3, and FADS3AT5 are undetectable. Transcripts involved in cellular process of translation, respiratory chain and ATP synthesis were the enriched functional gene groups identified in MFG. A lipid metabolism network using Ingenuity Pathway Analysis identified UBC as the outstanding interaction partner.Conclusion. To our knowledge this is the first report to show existence of evolutionarily conserved AT in MFG. We conclude that MFG may be a unique mRNA vector for the breast fed infant.Grant Funding Source: NIH R01AT007003
Selenium contents in Korean snack and dairy products (826.1)
Authors: Lee Okhee , Moon Jongwha , Chung Yongsam 
Published: June 2021

Se is a trace micro‐mineral and antioxidant protecting human body from the free radical induced lipid peroxidation. However, there are little reports on the Se intake status of Koreans because of deficient Se database on foods. Furthermore, the accuracy of existing data is questionable because they were usually analysed using methods as pre‐treatment process such as wet digestion or dry digestion, which can cause selenium loss. This study was aimed to evaluate Se contents in edible portion of snack and dairy products by instrumental activation analysis(=INAA) method using freeze‐drying as a pre‐treatment process. The most frequently consumed snacks and dairy products by Korean were selected for the analysis of Se contents. To minimize contamination, all the instruments and storage tools were used after washing with HNO3. Each food samples were individually mixed using homogenizer equipped with titanium blade. The homogenized food samples of 10~20g were freeze‐dried at temperature of ‐60 C for 24~96 h and subsequently, used to analyze Se contents by IINAA‐method. Analytical quality control was conducted using NIST SRMs. The analysis limit of Se in foods by INAA was 0.01ppm. Se contents in processed foods were in the range of 0.22ug~14.9ug in 100g foods. The Se contents were various according to the type of processed foods. The average Se contents in 100g sandwich, snack, milk, soy milk, joghurt were presented. This result will be useful in establishing the food Se database for Koreans.Grant Funding Source: Korean Research Foundation
Dietary uridine supplementation decreases tumor number in Apc(Min/+) mice (829.11)
Authors: Field Martha , Stover Patrick 
Published: June 2021

Colorectal cancer affects 1.23 million people and accounts for more than 600,000 deaths each year worldwide. Deficiency of methyl donors including folate and methionine has been linked to increased colon cancer risk in experimental and epidemiological studies. The Apc(Min/+) mouse model is a powerful tool for studying the genetic and dietary mechanisms which contribute to intestinal cancer phenotypes. A previous study showed that Apc(Min/+) mice also lacking one copy of the Shmt1 gene, which results in perturbed de novo thymidylate (dTMP) synthesis, displayed increased intestinal tumor number that was exacerbated by folate deficiency. dTMP is the only nucleotide that is synthesized at the replication fork as needed for DNA replication and repair. dTMP can either be synthesized de novo from the folate‐dependent reductive methylation of deoxyuridylate (dUMP) to dTMP through a multi‐enzyme complex or can be generated by phosphorylating thymidine to dTMP by the salvage pathway enzyme thymidine kinase (TK1). In this study, we sought to determine whether dietary supplementation of dTMP precursors (thymidine, deoxyuridine or uridine) could modify tumor number in the Apc(Min/+) model. Surprisingly, dietary uridine supplementation reduced intestinal tumor number and tumor burden by 40% (p<0.05) relative to the control diet; neither thymidine nor deoxyuridine affected tumor number.Grant Funding Source: Supported by NIH R37DK58144
Taurine may affect redox homeostasis via regulation of thioredoxin interacting protein in endothelial cells (830.29)
Authors: Vincent Andrew , Scheers Nathalie , Gabrielsson Britt , Sandberg Ann‐Sofie 
Published: June 2021

Taurine, a bioactive compound abundant in herring, has been shown to be active against endothelial dysfunction, through the alleviation of high‐glucose induced apoptosis and increased proliferation in endothelial cells. The nutrient‐sensitive inhibitor of anti‐oxidant defence, TXNIP, has been shown to be up‐regulated during endothelial dysfunction. Through ELISA and western blot analyses we have found that TXNIP levels are affected by taurine treatment in endothelial cells. The results indicate that dietary taurine may be important for maintaining redox homeostasis of endothelial cells.Grant Funding Source: Supported by The Swedish Council for Environment, Agricultural Sciences and Spatial Planning
Enigmatic chloride channels ő how to contribute to cerebrovascular remodeling (841.10)
Authors: Guan Yong‐Yuan , Wang Guan‐Lei 
Published: June 2021

TMEM16A and ClC‐3 are responsible for Ca2+ activated (CaCC) and volume‐regulated (VRCC) Cl‐ channels respectively in rat basilar smooth muscle cells (BASMCs). The activity of CaCC and TMEM16A expression in BASMCs isolated from 2‐kidney, 2‐clip (2K2C) hypertensive rats were decreased , and CaCC activity negatively correlated with the blood pressure and the medial cross sectional area in basilar artery during hypertension. Knockdown of TMEM16A facilitated, whereas, overexpression of TMEM16A inhibited, angiotensin II induced cell cycle transition and cell proliferation. TMEM16A affected cell cycle progression mainly through regulating the expression of cyclin D1 and cyclin E. These results indicated that TMEM16A CaCC is a negative regulator of cell proliferation. ClC‐3 expression and volume‐regulated Cl‐ movement were enhanced in BASMCs from 2K2C hypertensive rats. The Cl‐ movement was positively correlated with increase of blood pressure. Enhanced ClC‐3 channel activity in hypertension was closely associated with cerebrovascular structural remodelling. ClC‐3 evoked up‐regulation of cyclin D1 and cyclin E, and down‐regulation of p27KIP and p21CIP through Akt pathway, leading to cell cycle G1/S transition and cell proliferation. These results suggest that both VRCC and CACC mediate cerebrovascular remodeling by different mechanisms. It is still enigmatic that the interaction between TMEM16A and ClC‐3 Cl‐ channel in the development of cerebrovaascular remodeling.Grant Funding Source: Supported by National Natural Science Foundation of China (No.81230082,81370897,813111115)
The 2.7‐Å crystal structure of Gα12 in complex with a regulator of G protein signaling homology (RH) domain (843.1)
Authors: Kreutz Barry , Chanthavong Dara , Santarsiero Bernard , Kozasa Tohru 
Published: June 2021

Heterotrimeric G proteins Gα12 and Gα13 parse signals from G protein‐coupled receptors at the cell surface to activation of RhoA through a subset of RhoA‐specific exchange factors (RhoGEFs), including human proteins p115 RhoGEF, PDZ‐RhoGEF, and leukemia‐associated RhoGEF/LARG. Each of these proteins share a well‐conserved regulator of G protein signaling homology (RH) domain which binds with high affinity and specificity to active forms of Gα12 and Gα13. Concurrent with their activation as effectors, p115 RhoGEF and LARG were shown to function as GTPase‐activating proteins (GAPs) to downregulate Gα13, and to a lesser extent, Gα12, through direct stimulation of their rates of GTP hydrolysis. To identify the structural determinants of interaction between Gα12 and RH domain‐containing RhoGEFs, we purified and crystallized a 1:1 complex of an activated Gα i/12 chimera and the RH domain of p115 RhoGEF. The 2.7‐Å crystal structure of this complex was solved by molecular replacement. Detailed comparisons were made between the refined model and previously‐reported crystal structures of Gα13 in complex with the RH domain of either p115 RhoGEF or PDZ‐RhoGEF. The interaction surface of Gα12 and the p115 RhoGEF RH domain is bipartite and highly similar to that seen in Gα13:p115 RH domain complex structures. We are currently testing the hypothesis that the engagement of p115 RhoGEF by either Gα12 or Gα13 is differentially transmitted to residues involved in the mechanism of GTP hydrolysis, and this effect is primarily responsible for measured differences in GAP activity toward Gα12 and Gα13.Grant Funding Source: Supported by a grant from the National Institutes of Health GM061454 (to T.K.).
Targeting hepatic thioredoxin reductase by the acetaminophen metabolite N‐acetyl‐p‐benzoquinone (844.15)
Authors: Jan Yi‐Hua , Dragomir Ana‐Christina , Gardner Carol , Heck Diane , Laskin Debra , Laskin Jeffrey 
Published: June 2021

Acetaminophen is biotransformed by cytochrome P450's in hepatocytes to an electrophilic metabolite, N‐acetyl‐p‐benzoquinone imine (NAPQI). This reactive species is known to bind to glutathione and a variety of hepatic proteins, an important downstream event mediating acetaminophen hepatotoxicity. Mammalian thioredoxin reductase (TrxR) is a critical cellular antioxidant which contains a selenocysteine in its C‐terminal redox center, an accessible target for electrophilic modification. In the present studies, we characterized the reaction of NAPQI with TrxR. Acetaminophen treatment of mice (300 mg/kg, i.p.) caused a marked time‐dependent inhibition of the activities of both cytosolic TrxR1 and mitochondrial TrxR2. Using purified rat liver TrxR1, we found that inactivation of the enzyme was correlated with APAP metabolism by P450s. This suggested that enzyme inhibition was a result of the formation of reactive metabolites of acetaminophen. To examine the mechanism underlying the inhibitory actions of acetaminophen, the effects of NAPQI on purified TrxR were characterized. We found that NAPQI‐mediated enzyme inhibition required reduced TrxR. A recombinant mutant enzyme, in which selenocysteine was replaced with cysteine was only weakly inhibited by NAPQI indicating that selenocysteine residues in the redox motifs of the enzyme are critical for enzyme inactivation. This was supported by our findings that alkylation of TrxR with biotin‐conjugated iodoacetamide, which selectively reacts with selenol or thiol groups on proteins, was inhibited by NAPQI. Moreover, LC‐MS/MS analysis confirmed that NAPQI selectively modified cysteine 59, cysteine 497 and selenocysteine 498 residues in the redox centers of TrxR, resulting in enzyme inhibition. Collectively, these data demonstrate that reactive intermediates of acetaminophen can target TrxR demonstrating a novel mechanism by which this analgesic induces oxidative stress and hepatotoxicity.Grant Funding Source: Supported by AR055073, ES004738, CA132624, and ES005022.
The neuronal nitric oxide synthase inhibitor NANT blocks acetaminophen (APAP) toxicity in mouse hepatocytes (844.16)
Authors: Banerjee Sudip , Melnyk Stepan , Letzig Lynda , James Laura , Hinson Jack 
Published: June 2021

3‐Nitrotyrosine (3NT) in liver proteins of mice treated with hepatotoxic doses of APAP correlates with toxicity. Nitration is by peroxynitrite (ONOO‐), a reactive nitrogen species formed from nitric oxide (NO) and superoxide (O2‐). We postulated that APAP toxicity is mediated by peroxynitrite. Since iNOS knockout mice are equally susceptible to APAP toxicity as wildtype mice we examined the potential role of nNOS in APAP toxicity in hepatocytes using the specific nNOS inhibitor NANT (10µM) (N‐[(4S)‐4‐amino‐5‐[(2‐aminoethyl) amino] pentyl]‐N’‐nitroguanidine tris (trifluoroacetate)). Primary hepatocytes (1 million/ml) from B6C3F1 mouse were incubated with/without APAP (1mM). Every 0.5h 1million cells were removed and assayed spectrofluorometrically for NO and superoxide production using diaminofluorescein (DAF) and Mitosox, respectively. Cytotoxicity was determined by LDH release into media. Glutathione (GSH, GSSG), 3NT, GSNO and acetaminophen‐cysteine (APAP‐Cys) adducts were measured by HPLC‐EC. APAP significantly increased cytotoxicity at 1.5‐3.0h. The increase was blocked by NANT. NANT did not alter APAP mediated GSH depletion or covalent binding which indicated that NANT did not inhibit metabolism. APAP significantly increased NO and superoxide at 0.5 and 1.0h, respectively. The increases in both NO and superoxide were blocked by NANT. APAP significantly increased 3NT at 1.5‐3.0h and the increase was blocked by NANT. The data support the hypothesis that APAP hepatotoxicity is mediated by reactive nitrogen formed by nNOS.Grant Funding Source: NIH RO1 DK079008
Nicotinic acetylcholine receptors: expression demonstrates functional diversity in parasitic nematodes (844.4)
Authors: Buxton Samuel , Charvet Claude , Neveu Cedric , Robertson Alan , Martin Richard 
Published: June 2021

Nicotinic acetylcholine receptors mediate fast neurotransmission in both vertebrates and invertebrates. Selective targeting of parasite nAChR by antiparasitic drugs requires functional and/or structural differences between the receptors of the host and the parasite. Anti‐parasitic drugs like levamisole, pyrantel, tribendimidine, and derquantel (cholinergic anthelmintics) selectively target the nAChRs of nematodes. Unfortunately, regular use of anthelmintics has resulted in increasing reports of resistance in livestock parasites. Our aim has been to understand the molecular pharmacology of the nAChRs in parasitic nematodes, to inform development of better anthelmintics. We have cloned homologues of the nAChR subunit genes unc‐29, unc‐38, unc‐63 and acr‐8 from Oesophagostomum dentatum, a pig GI parasite. By employing the Xenopus laevis oocyte expression system, we demonstrated that four, pharmacologically different receptor subtypes can be reconstituted with various combinations of the four subunits. Single‐channel properties of one of the reconstituted receptor subtypes matched with one of the four subtypes recorded in vivo from O. dentatum, demonstrating the physiological relevance of the reconstituted receptor subtypes. Comparing these results with reconstitution results from other nematodes demonstrates the diverse, plastic nature of nAChRs in parasitic nematodes.Grant Funding Source: Supported by NIH R01 AI047194‐12, R21AI092185‐01 and Chateaubriand Fellowship
Consumption of diets high in fat and/or sucrose enhances the locomotor stimulatory effects of cocaine in male and female C57Bl/6J mice (848.7)
Authors: Collins Gregory , Chen Edward , Rush Elise , Chris Tcshumi , Koek Wouter , France Charles 
Published: June 2021

Drug abuse and obesity are serious public health problems. Dopamine systems play a central role in mediating the reinforcing effects of drugs and food, and the prolonged use of drugs or consumption of palatable food is known to alter the function and/or sensitivity of many neurotransmitter systems, including dopamine systems. The current studies evaluated the impact of consuming a high‐fat diet and/or a 10% sucrose solution on the sensitivity of adult mice (8 males and 8 females per condition) to the locomotor effects of cocaine (3.2‐32.0 mg/kg) across four weekly tests. The acute locomotor stimulatory effects of cocaine were enhanced in both male and female mice that consumed diets high in fat and/or sucrose, relative to mice that consumed standard chow and water. Although these diet‐induced enhancements generally persisted with repeated cocaine testing, sensitization to the locomotor effects of cocaine developed more rapidly in female mice drinking sucrose (and consuming either standard or high‐fat chow), relative to sex‐matched mice consuming standard chow and water; mice from all other feeding conditions developed sensitization at a rate comparable to their standard chow and water counterparts. The results of these studies provide clear evidence that consuming diets high in fat and/or sugar enhances cocaine effects in ways that might increase vulnerability to abuse cocaine.Grant Funding Source: Supported by K05 DA017918 and a Zannoni (SURF) Fellowship through ASPET