bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of young child overweight and obesity in the U.S.‐affiliated Pacific region: a meta analysis from the Children's Healthy Living Program (621.6)
Authors: Novotny Rachel , Fialkowski Marie , Li Fenfang , Vargo Donald , Paulino Yvette , Coleman Patricia , Bersamin Andrea , Nigg Claudio , Leslie Jodi , Leon Guerrero Rachael , Deenik Jonathan , Kim Jang , Wilkens Lynne 
Published: June 2021

A meta‐analysis of published literature and publicly available agency reports was conducted to estimate overweight and obesity prevalence of 2‐8 year (y) old US Affiliated Pacific (USAP) Region (USAP Islands, Hawai`i and Alaska) children. Contiguous US data served as reference. The search was limited to resources in English and 2‐8y on USAP children data from 2000 and newer and used CDC 2010 overweight and obesity reference data. USAP region sources (n=23) and NHANES articles (n=3; the contiguous U.S reference) were included. Data were disaggregated into single years of age. The children measured for the age group were divided equally and the prevalence was assigned to each individual age. A mixed model regressed the prevalence on a polynomial in age, accounting for the prevalence variance and another model compared jurisdictions. Overweight and obesity increased from 21.0% at 2y, to 39.2% at 8y (p<0.0001) for the USAP. In comparison, combined overweight and obesity increased from 24.2% at 2y to 34.8% at 8y (p<.0001) for NHANES. USAP data showed with a sharp increase in prevalence at 5y. Obesity alone increased from 10.2% at 2y, doubling to 23.6% at 8y (p<0.0001) whereas overweight prevalence was stable from 2y (12.6%) to 8y (14.6%). Jurisdiction differences were dramatic. Further examination of USAP young child obesity is needed.Grant Funding Source: Supported by USDA Grant 2011‐68001‐30335
Does exposure to whole grain foods change explicit and implicit wanting of food categories differing in sweet/savory and low/high fat? (631.5)
Authors: De Leon Angela , Rust Bret , Horn William , Burnett Dustin , Keim Nancy 
Published: June 2021

Understanding the complexity of food choice behavior has become paramount in our current obesigenic environment. Drivers of food choice include ‘liking’_the pleasure derived from tasting a food and ‘wanting’_how hard one is willing to work to acquire that food. We designed an intervention which provided whole grains (WG) to self‐reported low WG consumers (< 1 WG oz/d) to gauge the effect of WG exposure on explicit and implicit wanting for foods varying in sweet taste and fat content. Healthy adults were provided market baskets of WG products for use over 6 wk. We hypothesized that exposure to WG would change explicit and implicit wanting, by halo effect, of food categories with reduced sugar and fat content. To assess changes a computerized paired comparison test was administered pre‐ and post‐intervention. Both implicit and explicit wanting was greatest for high fat savory foods and least for low fat sweet foods (p< .0001). In this sample we were not able to detect and intervention effect on specific food categories for implicit or explicit wanting.Grant Funding Source: Supported by USDA 5306‐51530‐019‐00D.
Modulation of CD36 scavenger receptor expression by curcumin and vitamin E affects cellular uptake of lipids and bacteria (639.1)
Authors: Zingg Jean‐Marc , Nakagawa Kiyotaka , Azzi Angelo , Meydani Mohsen 
Published: June 2021

The CD36/FAT scavenger receptor/fatty acid translocase mediates uptake of fatty acids into various tissues. Other CD36 ligands include oxLDL, β‐amyloid, Plasmodium falciparum ‐infected erythrocytes, and bacteria. The ability of nutritional components to affect CD36 expression and to change the inflammatory and phagocytic response to lipids and bacteria in monocytes/macrophages could be important for modulating inflammation and atherosclerosis. Here we show that curcumin, a natural polyphenol from turmeric plant Curcuma longa, is rapidly taken up into cells and increases surface localization of CD36 leading to increased lipid uptake in THP‐1 monocytes/macrophages. The curcumin metabolite, tetrahydrocurcumin, has no effect, most likely since it is not efficiently taken up into cells. In contrast, CD36 surface localization and lipid uptake were decreased by α‐tocopherol and more so by α‐tocopheryl phosphate. Interestingly, phagocytosis of inactivated Staphylococcus aureus fluorescent bioparticles was affected by these compounds in a similar manner as observed for lipids, suggesting that binding and uptake of lipids and bacteria may share common molecular mechanisms. Thus, these dietary components may not only directly modulate the cellular anti‐microbial and inflammatory response but also indirectly by influencing host‐microbe interactions. Supported by USDA Contract #58‐1950‐0‐014.Grant Funding Source: Supported by USDA Contract #58‐1950‐0‐014.
The effect of a high vs. low glycemic response diet on the intra‐ and extracellular redox state (641.10)
Authors: Simmons Amber , Wong Siu , Corkey Barbara 
Published: June 2021

Increased consumption of processed foods is suspected to be contributing to obesity and chronic disease. We hypothesized that long‐term consumption of more processed food (mimicked with high (HGR) or low glycemic response (LGR) starches) would lead to oxidation of the circulating redox state, increased fat accumulation, and reduced insulin sensitivity. Mice consumed HGR or LGR food for 16 weeks. Body mass increased at a faster rate for those consuming the HGR diet (p < 0.05 for weeks 8‐16). Percentage body fat was greater and percentage lean mass was lower in the HGR group starting at 12 weeks (p < 0.05; MRI). However, insulin sensitivity at week 14 (OGTT; AUC, p = 0.14) and metabolic parameters (RER, heat production, activity) at weeks 4 or 15 were not significantly different between groups. At the termination of the study, redox pairs (L/P, B/A) suggested a more oxidized redox state in blood of mice on the LGR diet. TrxR activity in blood and TBARS of blood and liver tissues were similar between groups (p > 0.05). These data illustrate that the mechanism by which processed carbohydrates contributes to obesity is not via oxidation of the circulating redox state.Grant Funding Source: United States Department of Agriculture
Development of a relevant cell culture model to examine lutein absorption in vitro (645.12)
Authors: Kamil Alison , Blumberg Jeffrey , Chen C‐Y. 
Published: June 2021

Lutein bioavailability is influenced by dietary fat which facilitates absorption via micelles. Permeable support systems are employed in in vitro nutrient absorption studies but data are absent on whether this approach generates results more relevant to in vivo absorption than a monolayer system (MONO). We used Caco‐2 colorectal cells to compare the efficacy of lutein uptake in a MONO and a permeable support Transwell® system (TRAN) to examine the role of micelles. After plating for 2 and 21 d to attain confluence and differentiation in MONO and TRAN, respectively, cells were treated with 4 µg/mL lutein in 0.8% ethanol or synthetic micelles. After 36 h, lutein in cell lysate and basolateral medium was quantified by HPLC. Lutein in the cell lysate after ethanol was 220% greater than after micelle solubilization in MONO (3.0 vs. 1.4 µg/mg protein) but in the TRAN, lutein after ethanol was 77% lower (0.3 vs. 1.3). In TRAN, <1% (14.6 ng) of the micellized lutein was secreted to the basolateral medium while none was detected with lutein in ethanol. Thus, differentiation and/or culture system mediate lutein uptake into Caco‐2 and micelle components facilitate the intestinal secretion of lutein. As differentiated Caco‐2 display small intestinal phenotypes, micelles appear necessary to enable lutein transport across the small intestine but lutein can move into the large intestine efficiently without this facilitation.Grant Funding Source: Suported by USDA
FGF21 deficiency exacerbates chronic alcohol induced fatty liver disease via a p38MAPK and PGC‐1α mediated pathway (653.13)
Authors: Liu Yanlong , Zhao Cuiqing , Zhang Min , Wu Guicheng , McClain Craig , Feng Wenke 
Published: June 2021

Extrahepatic hormones, such as insulin and glucagon, are important in alcohol‐induced alteration in liver lipid metabolism. However, little is known whether the paracrine and endocrine signal for metabolic regulation of hepatic itself participates in alcohol exposure associated lipid accumulation. Fibroblast growth factor 21 (FGF21) is a hepatokine and plays a critical role in the glucose and lipid metabolism in obese and diabetic animals. Here, we demonstrated that FGF21 deficiency exacerbate chronic alcoholic liver disease (ALD). Mice were fed diet containing 5% alcohol for 4 weeks. Alcohol feeding increased hepatic fatty acid and triglyceride contents and fat accumulation in WT mice, which is exacerbated in FGF21‐KO mice. The increased hepatic steatosis was accompanied by elevated liver injury evaluated by liver enzyme levels and hepatic inflammation. Hepatocyte mitochondrial fatty acid β‐oxidation was reduced, as measured by Seahorse technology, and genes involved in the β‐oxidation were down‐regulated in FGF21‐KO mice exposed to alcohol. Further studies showed that alcohol exposure significantly decreased PGC‐1α phosphorylation and p38MAPK activation in FGF21‐KO mice. In vitro study showed that recombinant FGF21 treatment increased PGC‐1α activation, the effect was diminished by p38MAPK inhibitors. In conclusion, FGF21 is likely required for cellular capacity for fat clearance in subjects exposed to chronic alcohol through PGC‐1α activation.Grant Funding Source: Supported by NIH, DOD and Veterans Administration
Lipid‐derived aldehyde, acrolein, is a critical mediator of alcohol‐induced gut‐liver injury (653.14)
Authors: Chen Wei Yang , Zhang Jingwen , McClain Craig , Barve Shirish , Joshi‐Barve Swati 
Published: June 2021

Alcohol is the most socially accepted addictive drug which leads to alcoholic liver disease (ALD), a major cause of morbidity/mortality in the United States. Chronic alcohol consumption, commonly associated with cigarette smoking, causes a pro‐oxidant environment in the liver and increases lipid peroxidation. Acrolein (ACR) is the most reactive and hepatotoxic aldehyde metabolite generated via lipid peroxidation, and is a major component of cigarette smoke. This study investigates the pathogenic role of acrolein as a major mediator of intestinal barrier dysfunction and hepatic endoplasmic reticulum (ER) stress and injury, which are recognized etiologic factors in ALD.We examined hepatic and intestinal effects of acrolein and alcohol using in vitro (rat hepatic H4IIEC, and human intestinal epithelial Caco2 cells) and in vivo (C57/Bl6 mice ‐ chronic+binge alcohol feeding) models. ACR adducts accumulated in response to alcohol or ACR in mouse livers and intestines, and in cultured cells. This was accompanied by hepatic steatosis, activation of JNK, ER stress (upregulation of ATF3, ATF4, and pro‐apoptotic CHOP), mitochondrial disruption and apoptosis as seen by Cellomics. Notably, the cytotoxic effects of ACR and alcohol were attenuated by acrolein/aldehyde scavengers, and by an inhibitor of phosphodiesterase‐4 which regulates cellular cAMP. Alcohol‐induced in vivo intestinal effects (down‐regulation of tight junction proteins ZO‐1, occludin, and claudin, and barrier dysfunction) were mimicked by ACR in Caco2 cells. Our study demonstrates that acrolein is an important mediator of the hepatic and intestinal effects of alcohol consumption, and suggests a therapeutic potential for phosphodiesterase inhibitors and acrolein scavengers in ALD.Grant Funding Source: Supported by NIH, DOD and Veterans Administration
Pathogenic mechanisms in highly active anti‐retroviral therapy‐induced hepatotoxicity: role of phosphodieaterase 4 and ER‐stress (653.7)
Authors: Donde Hridgandh , Barve Priyanka , Barker David , Joshi‐Barve Swati , Gobejishvili Leila , McClain Craig , Barve Shirish 
Published: June 2021

HIV protease inhibitors (HIV‐PIs) are the major components of HAART and have been successfully used in the treatment of HIV‐1 infection in the past two decades. However, it has been shown that HIV‐PIs induce endoplasmic reticulum (ER) stress response and subsequent activation of unfolded protein response leading to dys‐regulation of hepatic lipid metabolism and hepatotoxicity. Our recent work shows that PDE4/cAMP metabolism plays a significant role in alcohol‐induced hepatic steatosis and injury. Hence in the present study, we examined the mechanisms underlying HIV‐PI induced hepatic ER stress and toxicity with a particular emphasis on PDE4 family of enzymes.The effects of clinically used HIV‐PIs (Ritonavir and Lopinavir) were examined both in a rat hepatoma cell line as well as rat primary hepatocytes. These studies demonstrated that PIs led to a significant loss of hepatocyte survival. Notably, inhibition of PDE4 by a specific PDE4‐inhibitor, rolipram, markedly attenuated hepatotoxicity induced by PIs. Mechanistic role of PDE4 showed that PDE4 inhibition significantly decreases the expression of the ER stress related proteins CHOP, ATF‐4 and ‐3 induced by PIs. Furthermore, examination of the PDE4/cAMP‐regulated downstream signaling demonstrated the involvement of Exchange proteins activated by cAMP (EPAC). Specifically, EPAC cAMP analogue downregulated the expression of the PI‐induced ER‐stress genes. These data identify a pathogenic/mechanistic role for PDE4 regulated cAMP‐EPAC in the development of HIV‐PI induced ER‐stress leading to hepatic steatosis and injury.Grant Funding Source: Supported by NIH, DOD and Veterans Administration
Reversal of flow direction enhances endothelial cell arteriogenic signaling (670.9)
Authors: Heuslein Joshua , Meisner Joshua , Price Richard 
Published: June 2021

The key initiating stimulus for arteriogenesis in the presence of an arterial occlusion is altered shear stress along collateral arterial pathways that bypass the occlusion. Femoral artery occlusion in the mouse leads to increased flow across all collateral arteries with some collateral segments also experiencing a reversal of flow direction. We have recently shown that these “flow reversed” segments exhibited a 4‐fold increase in leukocyte recruitment and demonstrated enhanced arteriogenesis in the gracilis collateral network. To test if endothelial cell sensitivity to the flow‐direction change was a key element of the enhanced arteriogenesis, we applied the measured the in vivo hemodynamic changes of the gracilis collateral network to cultured human umbilical vein endothelial cells (HUVECs) and performed genome‐wide transcriptional profiling and pathways analysis. Endothelial cells demonstrated a 10‐fold greater number of genes sensitive to the additional flow‐reversal stimulus, as well as a broad amplification of the gene expression patterns of cells only exposed to an increase in shear stress magnitude. Further, the addition of flow‐reversal activated many of the signaling pathways known to be key mediators of collateral growth (e.g. p38 MAPK, VEGF, HGF, PKC, and NF‐κB) when compared to steady shear stress control. These were not activated with increased shear stress alone. Microarray results were further validated by RT‐PCR of a subset of known pro‐arteriogenic genes (KLF2, eNOS, and ICAM‐1) which demonstrated an increased expression with flow reversal. These results are consistent with an increase in shear stress alone as insufficient to fully achieve the maximal activation of the arteriogenic pathway. Incorporation of directional reversal may, therefore, provide a more physiological stimulus for interrogating the central pathways that drive arteriogenesis thus leading toward novel, more effective therapeutic options.Grant Funding Source: Supported by NIH 5R01HL074082, NIH1R21HL098632, AHA 09PRE2060385 AHA 10GRNT3490001, NSF GRFP DGE‐131
Combined effects of hypoxia, carbon monoxide and impaired pulmonary gas exchange on O2 transport and aerobic capacity (708.5)
Authors: Crocker George , Jones James 
Published: June 2021

This study determined how three factors interact to limit cardiopulmonary O2 delivery, O2 extraction and maximal aerobic capacity (VO2max): 1) breathing hypoxic gas; 2) impairing pulmonary gas exchange; and 3) reducing circulatory capacitance for O2. Five goats ran on a treadmill at VO2max following oleic‐acid induced acute lung injury (ALI) or with no lung injury (NLI). Goats breathed normoxic or hypoxic inspired gas fractions (FIO2 0.21 or 0.12) with and without small amounts of CO to maintain carboxyhemoglobin fractions (FHbCO) of 0.02 or 0.30. Hypoxia and ALI induced hypoxemia and reduced O2 delivery by different mechanisms: hypoxia reduced alveolar O2 partial pressure (PO2), whereas, ALI increased alveolar‐arterial PO2 difference. Elevated FHbCO lowered O2 delivery by reducing circulatory capacitance for O2 and reduced O2 extraction by increasing hemoglobin (Hb) affinity for O2. All combinations of hypoxia, ALI and elevated FHbCO attenuated the reduction in VO2max compared to the sum of each treatment’s individual effects on VO2max when administered separately. Hypoxia and ALI administered in combination attenuated the reduction in O2 delivery without affecting O2 extraction. Elevated FHbCO and ALI attenuated the decrease in O2 delivery because increased arterial O2 saturation partially compensated for reduced circulatory capacitance. The addition of ALI to the combination of hypoxic gas and elevated FHbCO attenuated the decrease in VO2max because the decrease in O2 delivery was attenuated and O2 extraction synergistically increased. Results from this study are applicable to individuals, e.g., soldiers, rescue workers and miners, that experience traumatic lung injury while breathing hypoxic and CO‐containing gases associated with fires.Grant Funding Source: Supported by U.S. Army Medical Research and Materiel Command with L‐3 Communications/Jaycor.
Measuring changes in locomotor activity of freshwater prawn larvae in response to exposure to water contaminants using the ViewPoint software and video tracking system (728.25)
Authors: Crooke‐Rosado Jonathan , Rivera‐Cheverez Nilsa , Sosa‐Llorens Maria 
Published: June 2021

As the population grows, so does the drive for urbanization. Urbanization and the resulting anthropogenic activities have an impact on the quality of nearby water resources. Puerto Rico’s population density is one of the highest in the world. We seek to develop a protocol to measure how Puerto Rico´s high level of urban development has impacted the behavior and nervous system function of river fauna. We have started by recording movement trajectory and velocity of freshwater prawn larvae during five consecutive periods of 10‐minutes light/dark cycles, using ViewPoint´s Zebrabox. Larvae of Macrobrachium rosenbergii, a species raised through aquaculture in Puerto Rico, were more active during dark cycles, whereas those of M. carcinus, the prawn species found most commonly in Puerto Rico´s rivers, were more active during the light cycles. Recordings were then made before and after exposure to two contaminants found in Puerto Rico´s urban rivers, chromium (Cr3+) and dibutyl phthalate (DBP), in levels allowed by the EPA for drinking water. Exposure of M. rosenbergii larvae to Cr3+ did not produce any significant changes in locomotion, whereas exposure of M. carcinus larvae to DBP did, affecting parameters such as total distance travelled at slow and fast speeds. This protocol will continue to be used to test effects of other river contaminants on locomotion at various developmental stages of prawns.Grant Funding Source: Supported by: NSF HRD‐1137725; NIH NIGMS 5SC3GM084763
A suction blister model reliably assesses skin barrier restoration and immune response (734.1)
Authors: Smith Tracey , Montain Scott , Wilson Marques , Young Andrew 
Published: June 2021

This study assessed test‐retest reliability of a skin suction blister method for evaluating immune function. Up to 8 blisters (~30 mm2) were induced via suction on participant’s left and right forearm, separated by ~1 week. Fluid was sampled from blisters and the top layer was removed to reveal up to 8 wounds. Fluid was collected from wounds 4, 7 and 24 h post‐blistering, and pro‐inflammatory cytokines were measured. Transepidermal water loss, to assess skin barrier recovery, was measured daily until values were within 90% of unbroken skin. Sleep and stress (i.e., factors affecting wound healing), in the days before blistering, were assessed via activity monitors and the Perceived Stress Scale. This method was deemed reliable if correlations between the left and right arm reached 0.8. Skin barrier restoration for participants (n=16; 12M/4F; 23±5 years [mean±SD]) was 4.96±0.70 and 4.83±0.96 days for sessions 1 and 2, respectively. Correlations for skin barrier restoration, [area‐under‐the‐curve] IL‐6, IL‐8 and TNF‐α were 0.8, 0.9, 0.7, and 0.5, respectively (P<0.001‐P<0.05). When sleep and stress were considered, correlations improved for IL8 (0.8, P=0.002) and TNF‐α (0.7, P=0.01). This suction blister method is reliable for assessing skin barrier restoration and immune response, and can be used to study the functional impact of various stressors on immune function and wound healing.Grant Funding Source: Supported by the U.S. Army Medical Research & Materiel Command
Testing the versatility of the alternating sites of reactivity mechanism in the phosphagen kinases (768.11)
Authors: Aryal Manish , Snider Mark 
Published: June 2021

Phosphagen kinases achieve “buffering” of cellular ATP levels by catalyzing the reversible transfer of a phosphoryl group from ATP to a guanidino acceptor to form a high energy compound, phosphagen. Creatine kinase (CK), a PK found mainly in vertebrates, exists as a dimer in muscles; whereas, arginine kinase (AK), found exclusively in invertebrates, exists mainly as a monomer. The physiological functions of different oligomerization states within the PK family are not fully understood. Crystal structures of dimeric CK and AK are consistent with cooperativity in ligand binding between the two subunits. Based on these results, a reciprocating mechanism of catalysis was suggested for dimeric PKs. However, the exact mechanism and the potential effects of negative cooperativity on ligand binding ability of dimeric PKs remains unexplained. In this study, we’ve shown direct functional evidence of negative cooperativity in rabbit muscle CK (rbCK) by measuring the enzymes’ affinity for MgADP using isothermal titration calorimetry. Measurements of rbCK‐ligand interactions, in presence of saturating concentrations of creatine and nitrate, to form the transition‐state analogue quaternary complex, were fitted using a two‐site binding model with Kd1 = 56 ± 32 µM and Kd2 = 2.7 ± 1.4 mM. In the absence of creatine and nitrate, MgADP binding by rbCK fits a one‐site binding model, with Kd = 720 ± 330 µM. These suggest that the presence of creatine enables the conformation necessary to permit cross‐talk between the subunits. Pre‐steady state kinetic assays and the effect of viscosity on kcat show that the rate‐limiting step of reaction catalyzed by PKs is dependent on the oligomerization state of the enzyme, consistent with the alternating site of reactivity mechanism.Grant Funding Source: NSF Grant #0619123