bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between diet quality and cognitive control in childhood (124.1)
Authors: Khan Naiman , Raine Lauren , Drollette Eric , Scudder Mark , Cohen Neal , Kramer Arthur , Hillman Charles 
Published: June 2021

The influence of diet on specific aspects of cognitive function and brain health in childhood remains unknown. We aimed to investigate the relationship between diet quality and cognitive control in prepubertal children (8‐9‐years). Participants (N=58) completed a modified Eriksen flanker task assessing interference control. Healthy eating index (HEI) scores, based on 3‐day food records, were used to assess diet quality. Percent fat mass (%FM) and aerobic fitness were measured using DXA and VO2max, respectively. Partial correlations between HEI scores and flanker task performance (accuracy and reaction time [RT]) were conducted following adjustment of age, sex, SES, IQ, VO2max and %FM. HEI scores were not correlated with accuracy in the congruent task condition (r=0.12, p=0.20), RT in the congruent (r=0.19, p=0.08), and RT in the incongruent condition (r=0.18, p=0.09). However, HEI scores were positively correlated with accuracy during the incongruent condition (r=0.28, p=0.02) and negatively related to task interference (r=‐0.29, p=0.02). Given that the incongruent, relative to the congruent, task condition requires greater amounts of interference control, these data are among the first to indicate that higher diet quality may be important for upregulation of cognitive control when faced with higher cognitive demands in childhood.Grant Funding Source: Supported by NIH HD069381
Effect of oral nutritional supplementation on cognitive status in community dwelling elderly with sarcopenia and malnutrition (124.3)
Authors: Tian Min , Hustead Deborah , Mustad Vikkie 
Published: June 2021

Past research suggests that age‐related cognitive decline is associated with compromised nutritional and functional status. Much of this literature has focused on either institutionalized elderly or healthy community‐dwelling elderly. The purpose of this study was to determine whether oral nutritional supplementation (ONS) can improve cognitive status in community‐dwelling older adults with malnutrition and sarcopenia.Older adults (N=285; 65‐95 yrs) from 8 countries across Europe and North America completed a 24‐week ONS intervention trial. Sarcopenia was determined using the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Cognitive status was assessed by Mini‐Mental State Exam (MMSE).MMSE scores did not change significantly in the overall study population. In a subgroup of malnourished, sarcopenic older adults who began the intervention with cognitive impairment (MMSE score 蠄 26, n = 74), MMSE scores significantly improved from baseline to 12 weeks (p = 0.004) and from baseline to 24 weeks (p = 0.03). These data demonstrated that in community elderly with malnutrition and sarcopenia, ONS maintained cognitive status and even improved cognitive status in the subgroup with cognitive impairment.Grant Funding Source: Supported by Abbott Nutrition
Nutrient biomarker patterns and cognitive decline in older adults (124.6)
Authors: Bowman Gene , Mattek Nora , Dodge Hiroko , Quinn Joseph , Howieson Diane , Kaye Jeffrey 
Published: June 2021

We previously identified distinct nutrient biomarker patterns associated with both psychometric and neuroimaging indices of brain health in a cross‐sectional analysis of older adults. Those results propose that certain nutritional combinations influence global cognitive capacity, but also some relationships were more discrete and mapped to specific domains of cognition. The objective of this study was to determine if attention/working memory, episodic memory, and executive function decline is explained by nutrient biomarker patterns.Attention/Working memory (Digit Span Forward + Backward), episodic memory (CERAD) and executive function (Trails B + category fluency) Z scores were constructed. Nutrient biomarker pattern analysis of 30 biological markers of diet generated distinct nutrient biomarker patterns. Mixed‐effects estimated cognitive Z‐score change explained by the nutrient biomarker patterns.Eighty‐five non‐demented adults (53 women) with complete data had a mean age and duration of follow up of 86.4 (±10.4) and 4.6 (±1.8) years, respectively. One nutrient biomarker pattern representing a combination of eicosapentaenoic acid (20:5n‐3), docosahexaenoic acid (22:6n‐3), 25‐hydroxyvitamin D and pyridoxal 5‐phosphate was associated with less attention/working memory (AWM) decline after full adjustment (age, gender, education, ApoE genotype, hypertension, depression, baseline cognitive status, p=0.0099), however, these nutrients in isolation were not significant. Episodic memory and executive decline were not explained by the nutrient biomarker patterns.NBP analysis is one fruitful strategy for assessing the relationship between nutritional combinations and cognitive aging. These results suggest that long chain n‐3 PUFAs, vitamins D and B6 can jointly, but not independently prevent age‐related AWM decline. These results also highlight that indeed some aspects of cognition appear more sensitive to nutritional influence than others.Grant Funding Source: Supported by NCCAM AT004777 (GLB) NIA AG043398 (GLB), NIA‐AG08017 (JAK)
Lactation sufficiency is predicted by fasting plasma glucose at 1 month postpartum (131.1)
Authors: Nommsen‐Rivers Laurie , Glueck Charles , Huang Bin , Wang Ping , Dolan Lawrence 
Published: June 2021

We examined if postpartum metabolic health predicts lactation sufficiency. N=14 healthy mothers were enrolled during their maternity stay and followed up at 4 days (interview) and 1 month (interview, anthropometry and oral glucose tolerance test). The cohort had strong intentions to exclusively breastfeed but were overweight or obese (BMI, 33 + 5). Milk supply was grouped as: ABUNDANT, N=5, exclusively breastfeeding since birth with no milk supply concerns at either interview; SUFFICIENT, N=5, exclusively breastfeeding at 1 month but reported either delayed lactogenesis or current milk supply concern; and INSUFFICIENT, N=4, despite effort, unable to exclusively breastfeed. BMI, fasting insulin, insulin resistance index, and fasting plasma glucose (FPG) were all significantly lower in the ABUNDANT as compared to the SUFFICIENT or INSUFFICIENT groups (P‐value, 0.0003 to 0.03), but the strongest independent predictor of milk supply was FPG (P<0.0003). None in the abundant or sufficient, but 75% in the insufficient group, had impaired glycemia (FPG, 95 ‐ 125 g/dL) suggesting waning insulin secretion in the face of insulin resistance may be an important contributor to low milk supply.Grant Funding Source: Supported by the Cincinnati Diabetes and Obesity Cener and NIH 8 UL1 TR000077
Creating a roadmap for educational scholarship (14.3)
Authors: O'Sullivan Patricia 
Published: June 2021

Creating a Roadmap for Educational Scholarship Planning ahead can help bring educational scholarship to dissemination. The attendees will review the steps and sequence of activities to take an idea from something of interest to one that can be disseminated. Careful attention will be paid to the considerations in the methods that will ensure a robust study. Guidance will be given concerning publication opportunities.Specific Objectives: At the end of the session, participants will have: 1. Identified the steps necessary to move an idea from inception to dissemination.2. Considered the different approaches to conducting educational scholarship.
Inhibition of platelet‐induced NETosis via disruption of CXCL4/CCL5‐heteromerformation ameliorates organ damage after in ventilator‐induced lung injury (146.3)
Authors: Herter Jan , Rossaint Jan , Soehnlein Oliver , Weber Christian , Stadtmann Anika , Block Helena , van Aken Hugo , Zarbock Alexander 
Published: June 2021

Platelet leukocyte interactions are a hallmark of inflammation. We here report that platelet induced formation of neutrophils extracellular traps (NETs) is crucial for neutrophil recruitment following ventilator induced lung injury (VILI) as the inhibition of NET formation by DNAse dampens the severity of VILI. Furthermore, administration of MKEY, a peptide reported to disrupt heterodimer formation of platelet derived CXCL4 and CCL5, or blocking antibodies against CXCL4 and/or CCL5 caused a decrease in neutrophil influx and organ damage that was comparable to DNAase treatment or platelet depletion. The combination of platelet‐depletion and MKEY or antibodies against CXCL4/CCL5 did not show additive effects. Taken together, our data indicates that platelet derived CXCL5/CCL5 heterodimer formation is critical for platelet induced NET‐formation contributes crucially to the pathogenesis of VILI.Grant Funding Source: Supported by DFG: AZ428/3‐1, AZ428/6‐1, SFB1009/A5 to AZ, HE6810/1‐1 to JH, IZKF: SEED01/12 to JR
Focal adhesion kinase (FAK)‐related non‐kinase (FRNK) negatively regulates eosinophil recruitment (146.4)
Authors: Sharma Ritu , Zhang Hong , Stevens Kasia , Colarusso Pina , Patel Kamala 
Published: June 2021

Focal adhesion kinase (FAK)‐related non‐kinase (FRNK) is an independently expressed protein containing the C‐terminal domain of FAK. A recent study showed that FRNK negatively regulates lung fibrosis. In this study we asked if FRNK could negatively regulate human eosinophil recruitment in response to IL‐4. Exogenous expression of FRNK blocked >90% of eosinophil firm adhesion and transmigration to IL‐4‐stimulated endothelial cells (HUVEC) under flow conditions. FRNK blocked eosinophil recruitment by preventing the transcription and translation of VCAM‐1 and eotaxin‐3 (CCL26), two proteins we previously showed were critical for eosinophil recruitment. GATA6 has been shown to regulate VCAM‐1 in response to TNF, but its role in IL‐4‐mediated VCAM‐1 expression is not known. We found the IL‐4 increased GATA6 expression and down‐regulating GATA6 with siRNA blocked VCAM‐1 expression and function. Expressing FRNK in HUVEC prevented GATA6 upregulation by IL‐4 suggesting that FRNK blocks VCAM‐1 expression through its actions on GATA6. FRNK can act directly by binding to target molecules or indirectly by displacing FAK at focal adhesions and blocking FAK’s kinase activity. To determine if FRNK was acting through FAK, we down‐regulated FAK with siRNA and found that knocking down FAK had no effect on GATA6, VCAM‐1 or CCL26 expression. These data suggest that FRNK acts independent of FAK to negatively regulate eosinophil recruitment.Grant Funding Source: Supported by the Canadian Institutes of Health Research
CD99 signals through soluble adenylyl cyclase to regulate leukocyte transendothelial migration (146.6)
Authors: Watson Richard , Muller William 
Published: June 2021

Transendothelial migration (TEM) is the process by which leukocytes extravasate out of the vasculature into the interstitium and is one the key steps of the inflammatory response. PECAM and CD99 are two critical proteins at the endothelial cell border that function sequentially to regulate TEM (PECAM upstream of CD99). These proteins partially reside in a novel, intracellular endothelial cell compartment, known as the Lateral Border Recycling Compartment (LBRC), which supplies the extravasating leukocyte with unligated proteins and membrane surface area to facilitate its movement across the endothelium, in a process called targeted recycling (TR). While much is known regarding the function of PECAM during TEM, very little is understood regarding how CD99 signals. The C‐terminal tail of CD99 is short (39AA) and contains no known signaling motifs. Blocking homophilic interaction of leukocyte CD99 with endothelial cell CD99 arrests leukocytes part way through the junctions; cross‐linking endothelial CD99 overcomes this block. Here we show that engagement of leukocyte CD99 with endothelial cell CD99 (or crosslinking CD99 on endothelial cells to mimic this) activates PKA via a soluble form of adenylyl cyclase, ADCY10 (sAC). Blocking either PKA or sAC, but not transmembrane adenylyl cyclase (tmAC), recapitulates the phenotype of CD99 arrest on TEM and also prevents crosslinking‐mediated restoration of CD99 blockade. Activation of PKA restores TR of LBRC membrane to the arrested leukocytes to overcome the CD99 blockade. Current research is focused on identifying the mediators downstream of PKA as well as the signaling events taking place between the cytoplasmic domain of CD99 and sAC.This research was supported by F30 HL116100‐01A1 to RLW and R21 HL102519, R01 HL046849, and R37 HL064774 to WAM.Grant Funding Source: NIH NRSA F30 HL116100‐01A1
Vesamicol, an inhibitor of vesicular acetylcholine transporter, causes apoptosis in human lung adenocarcinomas (151.3)
Authors: Dom Aaron , Brown Kathleen , Lau Jamie , Thornhill Brent , Crabtree Clayton , Witte Theodore , Hardman W , McNees Christopher , Stover Cody , Carpenter A , Chen Y , Dasgupta Piyali 
Published: June 2021

Clinical studies show that the development of lung adenocarcinomas (LACs) is correlated with smoking habits. Nicotine, the addictive component of cigarettes, accelerates human LAC proliferation through nicotinic acetylcholine receptors (nAChRs). Human LACs contain all of the cholinergic system proteins, including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT) and nAChRs. In the present study we show that nicotine upregulates VAChT and ChAT. Therefore, we hypothesized that VAChT antagonists, such as vesamicol, may abrogate the growth of human LACs. Vesamicol induced potent apoptosis of nicotine‐treated human LACs in cell culture and nude mice models. Vesamicol did not have any effect on EGF or IGF‐II‐induced growth of human LAC’s. The ablation of VAChT levels by siRNA methodology reversed the apoptotic activity of vesamicol. We also observed that vesamicol caused cell death by inhibiting Akt phosphorylation. Taken together, our data shows that inhibition of nicotine‐induced cholinergic pathway by agents such as vesamicol may be useful for the treatment of human LACs.Grant Funding Source: Supported by an NIH R15‐Area Grant, a FAMRI YCSA Grant, and WV INBRE
Searching for conformationally‐selective small molecule therapeutics using ion mobility‐mass spectrometry (227.1)
Authors: Ruotolo Brandon 
Published: June 2021

Mass Spectrometry (MS) plays a number of key roles in the discovery and development phases for modern pharmaceutical compounds. Historically, however, MS has had a relatively limited role the drug discovery process in comparison to high‐throughput fluorescence and radiometric screens. This picture may be changing, however, as many presumptive protein targets are coupled to human disease pathways through specific protein‐protein interactions and protein conformations, rather than through enzyme activities. This fact is driving the development of high‐throughput analytical tools that put a stronger emphasis on protein structure information.We have been actively developing nano‐electrospray ionization coupled to ion mobility‐mass spectrometry (IM‐MS) into such a tool. Our IM‐MS protocols include the collision induced unfolding (CIU) of proteins and complexes, which functions as a highly‐sensitive and selective analog of isothermal calorimetry for gas‐phase protein‐ligand complexes, able to characterize protein stabilities at low concentrations within mixtures. Here, we will present our latest results where we demonstrate the ability of this technology to detect activation state‐selective kinase inhibitors, evaluate key conformational changes within amyloid protein‐ligand complexes, and identify signatures associated with cooperative ligand binding within multiprotein assemblies.
Plasma high‐resolution metabolomic profiling reveals upregulation of specific resolvins in patients with pulmonary tuberculosis (248.3)
Authors: Frediani Jennifer , Jones Dean , Tukvadze Nestan , Sanikidze Eka , Kipiani Maia , Uppal Karan , Kurani Shaheen , Hebbar Gautam , Colas Romain , Dalli Jesmond , Serhan Charles , Tangpricha Vin , Blumberg Henry , Ziegler Thomas 
Published: June 2021

Background: Characterization of metabolites altered by tuberculosis (TB) disease may identify pathophysiologic pathways. Resolvins are lipid mediators derived from endogenous EPA and DHA critical for resolution of inflammation.Methods: Plasma samples from 17 patients (35±12 yrs old) with new pulmonary TB and 17 matched household contacts without TB (controls) were analyzed using high‐resolution LC‐MS. False discovery rate (FDR; q=0.05) and hierarchal cluster analysis was used to distinguish accurate mass ions (metabolites) significantly different between groups. The METLIN Metabolite Database was used to match ions to known metabolites. Identification of specific D‐series resolvins (RvD1 and RvD2) was confirmed by LC‐UV‐MS/MS.Results: Over 23,000 metabolites were detected in untargeted metabolomic analysis, of which 61 were significantly different between the two groups by FDR. Eight metabolite clusters were evident containing several metabolites quantitatively upregulated in patients with TB (e.g. glutamate, choline derivatives, anti‐TB drug metabolites and several lipids, including likely M. tb cell wall lipids and resolvins RvD1 and RvD2.Conclusions: This pilot study revealed metabolites that are upregulated during newly diagnosed TB potentially involved in pathogenesis. Upregulation of specific resolvins may mediate recovery from inflammation in TB disease.Grant Funding Source: Supported by grants from the National Institutes of Health Fogarty grants D43 TW007124
Alpha‐tocopherol supplementation in lactating women impacts stereoisomer distribution but not total tocopherol content (250.1)
Authors: Sherry Christina , Oliver Jeffery , Marriage Barbara 
Published: June 2021

Eighty‐eight lactating women were randomized in 3 groups: Synthetic, 101.2 IU dl‐alpha‐tocopherol; Mixed, 30 IU d‐alpha‐tocopherol + 50.6 IU dl‐alpha‐tocopherol; or Natural, 60 IU d‐alpha‐tocopherol to assess the effect of supplementation on lactating women. Breast milk and plasma tocopherols were assessed at the beginning and end of the study by HPLC. There were no differences in alpha, gamma, and delta‐tocopherol in breast milk and plasma or vitamin E intake. There was a significant correlation between breast milk and plasma gamma‐tocopherol (r=0.52, P<0.0001). RRR was the most abundant stereoisomer in breast milk and plasma and increased over time. The natural supplement had a 1.4 and 1.2‐fold (breast milk) and 1.5 and 1.2‐fold (plasma) increase in RRR (percent of total stereoisomers) compared to the synthetic and mixed groups, respectively (P<0.05). There was a 2.4 and 3.1‐fold decrease in the percent of synthetic stereoisomers (2S, RSS, RRS and RSR) in the natural group compared to the synthetic group, in breast milk and plasma, respectively, and a 1.3 and 1.5‐fold decrease in breast milk and plasma compared to the mixed group (P<0.05). Taken together, alpha‐tocopherol stereoisomers in breast milk and plasma of lactating women change according to the type of supplement consumed, and RRR had a greater impact on blunting synthetic stereoisomer distribution likely due to the high percentage of RRR in all groups.Grant Funding Source: Supported by Abbott Nutrition
Ketoisocaproic acid suppresses insulin‐stimulated glucose transport in parallel with activation of mTORC1 in muscle cells (258.1)
Authors: Moghei Mahshid , Tavajohi‐Fini Pegah , Adegoke Olasunkanmi 
Published: June 2021

High protein diets are sometimes prescribed in weight management interventions; however these diets and amino acids (AA) have been linked to insulin resistance. Much of the attention has been on the branched‐chain amino acid (BCAA) leucine because of its ability to activate the mammalian target of rapamycin complex 1 (mTORC1). This complex and its substrate (S6K1) are implicated in AA‐induced insulin resistance due to their inhibitory serine phosphorylation of insulin receptor substrate 1 (IRS1). Since AAs other than leucine are present in dietary proteins, we examined their roles. Valine suppressed insulin stimulated glucose uptake (Glu‐trans) in L6 myotubes by 47% (P<0.05) compared to a suppression of 22% observed with leucine. The effect was not due to a greater intracellular accumulation of valine. However, valine and leucine, but not isoleucine, increased phosphorylation of S6K1 (thr389) and IRS1 (ser612 (P<0.05)). This is consistent with a lack of effect of isoleucine on Glu‐trans. We also examined the effect of 2 metabolites of leucine, ketoisocaproic acid (KIC) and isovaleryl CoA. KIC, but not isovaleryl CoA, suppressed Glu‐trans by 25% (P<0.05) and increased S6K1 and IRS1 phosphorylation. Strikingly, AA other than the BCAA, especially arginine and glutamine, also suppressed Glu‐trans by 22‐47% (P<0.05). Inhibition of Glu‐trans was not always linked to mTORC1/S6K1 and IRS1 phosphorylation. We conclude that KIC may mediate the suppressive effects of leucine on insulin stimulated glucose transport, and that amino acids other than leucine can induce insulin resistance of glucose transport.Grant Funding Source: Supported by NSERC and Faculty of Health, York University
Remethylation with dietary methyl donors contributes a significant proportion of methionine for the synthesis of protein and creatine in neonatal piglets (258.3)
Authors: Robinson Jason , McBreairty Laura , Harding Scott , Randell Edward , Brunton Janet , Bertolo Robert 
Published: June 2021

Methionine is an essential amino acid that is in high demand in neonates for both protein synthesis and as the primary methyl donor for transmethylation (TM) reactions. The vast majority of methyl groups are used for synthesis of creatine (CR) and phosphatidylcholine (PC). The demethylated methionine can be remethylated by dietary methyl donors such as folate, choline and betaine, but to what extent is unclear. We hypothesized that these methyl donors provide a nutritionally significant proportion of available methionine for TM and protein synthesis. 4‐8 d old piglets were fed a diet devoid (n=8) or replete (n=7) of methyl donors at 80% of the methionine requirement; methionine and phenylalanine isotopes were infused to calculate flux to products. Whole body protein synthesis and breakdown were respectively, 15% (p<0.05) and 20% (p<0.04) lower during methyl deficiency, corresponding to a ~70% reduction in fractional protein synthesis (Ks) in muscle (p<0.03) and unchanged Ks in liver. Methyl deficiency also led to 25% lower hepatic TM to creatine (p<0.02), which was offset by a 2‐fold greater TM to PC (p<0.03), due to choline deficiency which increases PC synthesis via TM. In conclusion, dietary methyl donors can re‐synthesize a substantial proportion of methionine that is used primarily for protein synthesis and potentially growth.Grant Funding Source: Supported by CIHR