bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex‐specific and Obesity‐specific Association of Serum Uric Acid with Cognitive Function in Older Adults
Authors: Cheatham Carol L , Vazquez‐Vidal Itzel , Turski Christa L , Medlin Amanda , Millsap Grace , Voruganti V. Saroja 
Published: June 2021

Lower serum uric acid concentrations have been linked to cognitive dysfunction. Uric acid is an antioxidant that accounts for over half of the free radical scavenging activity in humans. Higher serum concentrations of uric acid have been associated with slower progression of several neurodegenerative diseases. On the other hand, elevated serum uric acid levels have been associated with poorer processing speed and executive functioning and greater white matter atrophy. Our aim in this study was to ascertain the relation between uric acid and cognitive function in older adults with mild cognitive decline (defined at 1–1.5 SD below the mean on the Montreal Cognitive Assessment, MoCA). Cognitive function was assessed using the MoCA and Cambridge Neuropsychological Test Automated Battery (CANTAB). Mean concentrations of serum uric acid in 107 individuals (mean age = 72.7 ± 4.3 years) were 5.9 ± 2.3 mg/dl; males had significantly higher uric acid concentrations (6.3 ± 1.1 mg/dl) compared to females (5.4 ± 1.1 mg/dl). Obese individuals’ concentrations were higher (6.2 ± 1.1 mg/dl) as compared to overweight (6.0 ± 1.1 mg/dl) and normal weight individuals (5.1 ± 1.2 mg/dl). Hyperuricemia (in males, serum uric acid > 7mg/dl and in females, serum uric acid > 6mg/dl) was present in 24% of the individuals. Compared with normouricemic individuals, hyperuricemic had significantly (p < 0.05) elevated serum triglyceride levels (122.1 ± 67 vs. 184.5 ± 152 mg/dl) and higher waist circumference (39.3 ±4 vs. 41.1 ± 3 in). Serum uric acid was positively correlated with BMI, waist circumference, serum creatinine, serum glucose, serum cholesterol ( p < 0.00001). Serum uric acid was negatively associated with MoCA scores (r2 = −0.23, p = 0.02). When stratified by sex, serum uric acid was positively associated with errors made on the CANTAB spatial working memory task (t = 2.6, p = 0.014) in men, but not in women. Similarly, when stratified by BMI, serum uric acid was positively associated with spatial working memory errors (t = 2.9, p = 0.013) and rapid visual processing errors (t = 3.0, p = 0.01) from the CANTAB in obese individuals but not in normal or overweight individuals. In summary, among older adults, higher serum uric acid concentrations are linked to poorer cognitive function in all individuals, poorer spatial working memory in men and obese individuals, and poorer processing in obese individuals compared to other groups. These findings indicate a potential role for serum uric acid concentrations in cognitive function in older adults.Support or Funding InformationThis research was funded by grants from the United States Department of Agriculture (2010‐2342‐02 and 2015‐2809‐01) to the first author and a small grant from the Nutrition Research Institute to the first and last authors.
Susceptibility to sickle cell co‐morbidities is regulated by single nucleotide polymorphisms of the TOLLIP gene
Authors: Agyingi Smith , Donkor Akua , Thomas Bolaji 
Published: June 2021

Infectious diseases, despite the availability of vaccines, remain a challenge for sickle cell disease (SCD) patients. This is exacerbated in developing countries with high disease rates, poor hospital infrastructures and preponderance of co‐morbidities, complicating SCD case management. Therefore, elucidating the role of pathogen recognition factors or signaling pathways in immune response is critical in clarifying genes regulating infectious co‐morbidities. We have shown that the dysregulated immune response observed in SCD is not attributable to dendritic cells (CD209 gene promoter polymorphism) or Toll‐like receptor (TLR‐4 polymorphisms). Though there is a significant difference in CD209 gene promoter polymorphism between groups, it does not explain infection overload in African but not African American SCD patients. Toll‐interacting protein (TOLLIP) regulates human TLR signaling pathways, and its polymorphisms have been associated with infectious diseases. To decipher whether TOLLIP polymorphisms affect immune response upstream of TLR‐4 signaling, we examined the genetic diversity of TOLLIP polymorphisms (rs5743899 and rs3750920) within and between control (230, 379 and 159 Africans, African Americans and Caucasians respectively) and disease groups (145 and 331 African and African Americans respectively), utilizing a polymerase chain reaction and restriction fragment length polymorphism assay. We found significant interethnic disparity in the genotypic frequency (15.2%, 21.6% and 2.5%) of rs5743899 mutant variant between Africans, African Americans and Caucasians respectively. In addition, we also found a significant difference for rs5743899 mutant variant between disease and control groups in Africa (22.7% versus 15.2%) but not in the United States (23.3% versus 21.6%), with no difference between sickle cell disease groups. This observation shows that Tollip gene rs5743899 mutant variant is a potential contributor to predisposing sickle cell patients but not control groups in Africa to infectious co‐morbidities, and may explain the high levels of circulating immune complexes in disease groups. This report reveals interethnic susceptibility to infectious co‐morbidities and how this contributes to immune response in sickle cell disease.Support or Funding InformationRIT Louis Stokes Alliance for Minority Participation Fellowship (NSF Award #25901‐03200‐S01) (SEA)Laboratory Support Fund, College of Health Sciences and Technology (BNT)
After Oxidation Zinc Nanoparticles Lose the Ability to Enhance Responses to Odorant
Authors: Singletary Melissa , Daniels Yasmine , Hagerty Samantha , Pustovyy Oleg , Globa Ludmila , MacCrehan William A , Morrison Edward E , Sorokulova Iryna , Vodyanoy Vitaly J 
Published: June 2021

Previous studies have demonstrated that 1–2 nm zinc metal nanoparticles at small concentrations can enhance electroolfactogram (EOG) responses to the odorant. Introducing these particles to an odorant can increase responses up to 3‐fold1. Small zinc nanoparticles are comprised of only ≈60 metal atoms and, therefore, their stability in water is under consideration. The possibility that zinc nanoparticles enhance olfactory responses after oxidation is unknown. Zinc metal nanoparticles were produced from bulk metal rods by an underwater high‐voltage discharge method. Part of the small zinc nanoparticles were oxidized by percolating of air through the water suspension of nanoparticles. NIST zinc oxide nanoparticles of 15 and 70 nm 2 were also used in olfactory experiments. Odorant responses were evoked by the odorant mixture of ethyl butyrate, eugenol, and (+) and (−) carvone combined with metal or metal oxide nanoparticles. The EOG was recorded with isolated rat olfactory epithelium. The metal nanoparticles were characterized by atomic force microscope (AFM) and X‐ray photoelectron spectroscopy (XPS). AFM revealed size distributions of small Zn metal nanoparticles, with average diameters of 1.2 ± 0.3 nm. The XPS high‐resolution 2p3/2 spectra for zinc and zinc oxide revealed 93.9 ± 3.4 % and 5.9 ± 3.7 % of Zn and ZnO, respectively. This data indicated that more than 93 % of Zn atoms were not oxidized. EOG evoked by odorant mixed with small Zn nanoparticles, small and large ZnO nanoparticles showed that only small non‐oxidized Zn nanoparticles enhanced odorant responses. None of the particles delivered without odorant produced olfactory responses. This experimental evidence strongly supports our observations of the influence of Zn metal nanoparticle size on the enhancement of olfactory odorant responses. It has been suggested that the most critical property depending on metal particle size is its ability to donate and accept electrons3. A large number of small stable metal Zn nanoparticles were found in human and animal blood 4. We speculate that Zn nanoparticles function as electron donors in the Turin's model of olfaction5.Support or Funding InformationGrant from the National Institute of Standards and Technology: 70NANB14H324
Intermittent Hypoxia Enhances Connectivity between Cervical Spinal Interneurons
Authors: Streeter Kristi , Sunshine Michael , Patel Shreya , Reier Paul , Baekey David , Fuller David 
Published: June 2021

Intermittent hypoxia is a potent initiator of spinal plasticity and a promising rehabilitative modality to enhance respiratory and non‐respiratory motor function in certain cases of neurologic dysfunction. Current models of intermittent hypoxia‐induced spinal plasticity have focused exclusively on motoneurons, and nothing is known about how cervical spinal interneurons are impacted by intermittent hypoxia. Prior work has established that most cervical spinal interneurons alter discharge rates during acute hypoxia, and that some spinal interneurons are synaptically coupled with phrenic motoneurons. We hypothesize that acute intermittent hypoxia triggers “network level” spinal plasticity which manifests as an increase in the prevalence of temporally related discharge of spinal interneurons. To test this hypothesis, bilateral phrenic motor output was recorded in N=12 anesthetized and ventilated adult rats and a 16‐channel multi‐electrode array was used to record mid‐cervical neuron activity during and following three, 5‐min episodes of hypoxia (11% O2). To evaluate “functional connectivity” among spinal interneurons, cross‐correlation histograms were constructed for all possible pairs of simultaneously recorded neurons. A positive correlogram “peak” > 3 stdev above the mean was taken to indicate an excitatory connection. The current analysis focused on post‐hypoxia discharge, and data were included for 319 neuronal pairs in which a correlogram peak was detected during any post‐hypoxia period. A correlogram peak was present in 24% of neuronal pairs during the pre‐hypoxia baseline. This value tended to increase during hypoxia (Hypoxia‐1: 34%; Hypoxia‐2: 30%; Hypoxia‐3: 34%), but this did not reach statistical significance (all P>0.05 vs. baseline). In contrast, the number of excitatory connections, as reflected by positive correlogram peaks, were significantly increased following each bout of hypoxia (Hypoxia‐1: 60%; Hypoxia‐2: 53%; Hypoxia‐3: 50%) (all P<0.05 vs. baseline). This is the first demonstration that intermittent hypoxia alters the connectivity of spinal networks and we therefore conclude that the spinal impact of intermittent hypoxia extends beyond phrenic motoneurons. These data support the hypothesis that neuroplasticity in spinal networks contributes to sustained changes in respiratory and/or autonomic output following intermittent hypoxia.Support or Funding InformationNIH: 1F32NS095620‐01 (KS); 1R01NS080180‐01A1 (DF); and T32‐ND043730 (MS). Department of Defense W81XWH‐14‐1‐0625 (PR).
Sugar‐Sweetened Beverage Consumption in Young Adults: Understanding Eating Occasion Contextual Factors
Authors: McNaughton Sarah A , Leech Rebecca M , Pendergast Felicity J , Worsley Anthony 
Published: June 2021

Background/ObjectivesYoung adulthood represents an influential transitional period, marked by poor dietary habits and excess weight gain. Sugar‐sweetened beverages (SSBs) are a major source of excess caloric intake among young adults, yet little is known about the correlates of SSB consumption. This study examines the correlates of SSB consumption including eating occasion contextual factors, using real‐time assessment of young adults' eating occasions (EOs).MethodsData were collected during the Measuring Meals in Everyday Life (MEALS) study (n=557, adults 18–30 years). Participants reported all foods and beverages consumed over 3–4 non‐consecutive days using a food diary recorded via a Smartphone app. Contextual characteristics such as eating location, purchase location, presence of others and activities while eating were documented in the app at each EO. Information on sociodemographic factors and health behaviours were collected via an online questionnaire. An “eating occasion” was defined as an occasion when any food or beverage was ingested, while a “sugar‐sweetened beverage occasion” was defined as any EO where a SSB was consumed (with or without other items). SSB consumers were categorised as low or high SSB consumers based on the median frequency of consumption. Associations for individual level and EO level characteristics with level of SSB consumption were analysed using multivariate logistic regression, accounting for the clustered nature of the data.ResultsOverall, 30% of participants consumed SSBs. Most SSBs were consumed: either alone (43%) or with family/partner (42%); at home (50%), and while undertaking screen‐based activities (46%). Most SSBs consumed were purchased from the supermarket/grocery store (58%). Compared to non‐consumers, SSB consumers had a significantly higher BMI (mean [SD]: 23.1 [5.7] v 21.8 [3.9], P<0.001). Being a current/past smoker, being overweight/obese and participating in screen‐based activities were associated with being a high SSB consumer (P<0.01). After adjustment for covariates, smoking status (OR [95% CI]=5.69 [1.98,16.31]; P<0.01) and weight status (2.31 [1.06,5.01]; P<0.05) remained significantly associated with high SSB consumption.ConclusionsAlmost a third of young adults in this study consumed SSBs and most SSBs were consumed alone or with family/partner, at home and while undertaking screen‐based activities. However, individual factors, rather than EO contextual factors, were more strongly associated with being a high SSB consumer. Future research is needed to explore how SSB occasions differ from other beverage consumption occasions in relation to their accompanying foods and contextual characteristics.Support or Funding InformationAustralian Research Council, Victorian Health Promotion Foundation, National Health and Medical Research Council
Depletion of Dietary Bovine Milk Exosomes Impairs Sensorimotor Gating and Spatial Learning in C57BL/6 Mice
Authors: Mutai Ezra , Zhou Fang , Zempleni Janos 
Published: June 2021

BackgroundBovine milk exosomes contain cargos such as miRNAs, mRNAs, DNA and proteins. We have demonstrated that dietary bovine exosomes deliver functional RNA species and regulate genes and metabolism in humans and other non‐bovine species. Preliminary studies suggest that RNAs obtained through milk exosomes accumulate in the brain of mice.HypothesisDepletion of dietary bovine milk exosomes affects cognitive performance in C57BL/6 mice.MethodsC57BL/6 mice were fed AIN‐93G based, bovine milk exosome‐defined diets for up to 20 weeks. Exosome‐depleted diets are denoted E−; exosome‐sufficient controls are denoted E+. Spatial learning and memory were assessed using the Barnes maze and Morris water maze. Sensorimotor gating was assessed using an acoustic startle response (ASR) system. The statistical significance of differences was assessed by unpaired, two‐tailed t‐test.ResultsThe time needed to locate the escape hole in the Barnes maze increased by up to 130% in mice fed the E− diet compared to E+ controls (Fig. 1). Likewise, the time needed to locate and reach the submerged escape platform in the Morris water maze was significantly greater in female mice fed E− diet than female controls (Fig. 2). Prepulse inhibition (PPI) of the ASR is a measure of sensorimotor gating, and was significantly lower in female mice fed the E− diet than in female controls (Fig. 3). Diet did not affect PPI in male mice (p>0.05).Conclusion & future plansDiets defined by their content of bovine milk exosomes affect sensorimotor gating and cognitive performance in mice. Future studies will investigate which regions and cells in the brain accumulate dietary milk exosome RNA cargos, and whether a distinct species of RNA is responsible for the phenotypes reported here.Support or Funding InformationSupport: NIFA 2015‐67017‐23181, NIFA 2016‐67001‐25301/NIH DK107264, NIH 1P20GM104320, the Gerber Foundation, and USDA Hatch Act and W3002.
Functional characterization of three GH10 xylanases
Authors: Park Jesslyn , Glasgow Evan , Fox Brian G 
Published: June 2021

Decreased availability of fossil fuels has driven an increased demand for sustainable energy sources such as biofuels. One area of bioenergy research involves development of biocatalysts able to efficiently degrade biomass “waste”‐products, such as substrates derived from corn stover, rather than easily‐fermentable biomass used for food, such as starch from corn kernels. Xylanases are of interest for their ability to hydrolyze hemicellulosic sugars found in plant cell walls, allowing utilization of waste‐derived biomass. In this study, three xylanases of glycoside hydrolase family 10 (GH10) are functionally characterized and optimized for temperature and pH, as well as kinetically analyzed for xylose monomer and oligomer production. These enzymes, GH10‐4, GH10‐9, and GH10‐15, demonstrate activity upon substrates xylan and arabinoxylan. For GH10‐4, optima are 50°C at pH 8 on xylan and 45°C at pH 8 on arabinoxylan. For GH10‐9, optima are 70°C at pH 5 on xylan and 70°C at pH 5 on arabinoxylan. For GH10‐15, optima are 50°C at pH 8 on xylan and 45°C at pH 5 on arabinoxylan. Kinetic analysis reveals GH10‐4 produces xylose (X1), xylobiose (X2), xylotriose (X3), xylotetraose (X4), and xylopentaose (X5) from xylan, while GH10‐9 and GH10‐15 produce X1, X2, and X3. From arabinoxylan, GH10‐4 produces X1, X2, X3, X4, while GH10‐9 and GH10‐15 produce X1, X2, X3. Conclusive kinetic data may suggest applicability of these enzymes for industrial use within biocatalysts and contribute further insight to the functionality of enzymes within GH10.Support or Funding InformationThe authors are grateful for financial support by the Integrated Biological Sciences Summer Research Program (IBS‐SRP, NSF) at the University of Wisconsin‐Madison and the Great Lakes Bioenergy Research Center (GLBRC) of the U.S. Department of Energy. Presentation travel support is provided by the Ronald E. McNair Scholars Program of Winthrop University. The authors also thank Lai Bergeman, Craig Bingman, Bob Smith, Emily Beebe, Kirk Vander Meulen, Amber Smith, David Wassarman, and John Greenler for professional support.
Temperature‐Induced Changes to Aquaporin Localization in the Freeze‐Tolerant Cope's Gray Treefrog
Authors: Stogsdill Brian , Frisbie James , Krane Carissa , Goldstein David 
Published: June 2021

Cope's gray treefrogs alter their physiology in response to cold as part of their freeze tolerance mechanism. One such change involves the accumulation, both extracellularly and intracellularly, of cryoprotective glycerol, which likely crosses cellular membranes using glycerol‐permeable channels called aquaglyceroporins (GLPs). Three GLPs (HC‐3, HC‐7, and HC‐9) have been identified in the Cope's gray treefrog, representing homologs to the mammalian AQP3, AQP7, and AQP9, respectively.Regulation of transmembrane glycerol diffusion depends on GLP expression in the plasma membrane resulting from changes to transcriptional and translational output of the GLPs and/or by changes in protein trafficking to the plasma membrane. We have previously reported that GLP mRNA and protein expression are modulated during cold acclimation and freezing; however, localization of GLP proteins in the plasma membrane has not been studied thoroughly. We hypothesized that changes in acclimation temperature would alter the localization of the GLPs HC‐3 and HC‐9 in the plasma membrane and confirmed this with immunofluorescence, plasma membrane fractionation, and biotinylation.For HC‐9 in liver, quantitation of protein expression (by immunoblot) showed a 4‐ to 6‐fold increase in the higher molecular weight band of frozen (−2.5°C for 24 hours) and thawed (5°C for 24 hours after freezing) over warm (20°C) treefrogs. In immunohistochemistry images, HC‐9 signal appeared to be localized to the plasma membrane of hepatocytes of warm‐ and cold‐acclimated animals but dispersed intracellularly in frozen treefrog hepatocytes. In preliminary studies, fractionation of cellular protein (Biovision, Milpitas, CA) indicated that between freezing and thawing, the nominal (~34 kDa) molecular weight band of HC‐9 diminishes in the plasma membrane fraction while the (putatively) glycosylated high molecular weight band of HC‐9 increases.For HC‐3 in erythrocytes, protein expression is enhanced by cold acclimation and by incubation in medium containing glycerol. We incubated erythrocytes taken from warm‐acclimated animals at 4°C for 48 hours and biotinylated the surface proteins. In immunoblots of the biotinylated fraction probed with anti‐HC‐3 primary antibody, the high molecular weight (glycosylated) band was enriched and the nominal (~32 kDa) molecular weight band was diminished. These results suggest that water and glycerol permeability during cold acclimation and freezing can be modulated by protein trafficking, which may be influenced by the post‐translational modification of glycosylation.Support or Funding InformationSupported by NSF IOS‐1121457.
Undergraduate Student Research in Quantitative Analysis of Transcription Elongation Perturbation Networks Using Mass Spectrometry
Authors: Bedard Lynn , Boyd Asha , Dyer Nichole , Golay Zachary , Smith‐Kinnaman Whitney , Alakhras Nada , Mosley Amber L 
Published: June 2021

The main goal of this project is to identify how cells respond and adapt to genetic changes that alter the process of RNA synthesis. Using baker's yeast as the study system, experimental approaches provide undergraduate students with early exposure to cutting‐edge research technologies that are broadly applicable in both academia and industry. The project introduces students at all levels of training to the importance of quantitative methods to interrogate biology. The specific focus of the research is to understand the consequences of genetic perturbations that knock out or reduce expression of non‐essential elongation factors on RNA polymerase II‐catalyzed RNA synthesis (transcription). Preliminary data suggest that such genetic perturbations lead to significant adaptations within the RNA polymerase II protein‐protein interaction networks. These adaptations may include (but are not limited to) disruption of interactions with RNA polymerase II, compensation leading to novel protein recruitment, and activation of rescue pathways to dispose of arrested RNA polymerase II. The laboratory portion of an undergraduate course in molecular biology was redesigned to generate elongation factor knock‐out yeast strains with a focus on key molecular biology concepts and techniques including: genomic DNA isolation, oligonucleotide design, PCR, genotyping, protein isolation, and western blotting. In addition to these key concepts, we introduced students to the theory and practice of proteomics analysis through mass spectrometry including discussions of bioinformatics analysis of proteomics data, calculation of false discovery rates, and affinity purification mass spectrometry approaches. Thus far in this study, 9 elongation factor knock out strains have been made and verified by DNA sequencing and are in the process of being analyzed by quantitative mass spectrometry. Data from pre‐ and post‐instructional tests will be presented which demonstrate increased student understanding of mass spectrometry. Additionally, students participated in an 8 week summer internship held at the IU School of Medicine where they extended the project from the classroom lab to performing quantitative mass spectrometry analysis of their elongation factor knock‐outs.Support or Funding InformationDePauw University Student Faculty Research Fund, Showalter Fund (IU), NSF Award Number:1515748 PI Amber Mosley, PhD