bluuebunny/crossref_metadata_2025 huggingface dataset:
Apremilast monotherapy for long-term treatment of active psoriatic arthritis in DMARD-naïve patients
Authors: Wells Alvin F , Edwards Christopher J , Kivitz Alan J , Bird Paul , Guerette Benoit , Delev Nikolay , Paris Maria , Teng Lichen , Aelion Jacob A
Published: June 2021

Objectives

Apremilast monotherapy was evaluated up to 5 years in PALACE 4 (fourth PsA Long-term Assessment of Clinical Efficacy study) DMARD-naïve patients with PsA.

Methods

Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg or apremilast 20 mg twice a day. Placebo patients were rerandomized to apremilast at week 16 or 24. Double-blind apremilast continued to week 52, with a 4-year open-label extension (≤260 weeks of exposure). Analyses through week 260 were based on observed data.

Results

A total of 527 patients were treated. Among patients randomized to apremilast 30 mg at baseline, 45.5% completed week 260. At study end, 24.8% reported conventional synthetic DMARD or steroid use for any reason. At week 260, 65.8%/39.0%/20.3% of apremilast 30 mg patients achieved ACR20/ACR50/ACR70 responses, respectively. PsA sign and symptom improvements were sustained up to week 260 with continued treatment, including reductions in swollen (84.8%) and tender (76.4%) joint counts. Among apremilast 30 mg patients with baseline enthesitis or dactylitis, 71.2% achieved a Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 95.1% achieved a dactylitis count of 0. Over 50% of patients achieved a HAQ Disability Index minimal clinically important difference (≥0.35). In patients with ≥3% baseline psoriasis-involved body surface area, 60.3% and 47.6% achieved ≥50% and ≥75% improvement in Psoriasis Area and Severity Index scores, respectively. Patients continuing apremilast 20 mg also demonstrated consistent, sustained improvements. The most common adverse events were diarrhoea, nausea, headache, upper respiratory tract infection and nasopharyngitis. No new safety concerns were observed long term.

Conclusions

Apremilast led to sustained PsA efficacy up to 260 weeks and was well tolerated.

Trial registration

ClinicalTrials.gov (http://clinicaltrials.gov), NCT01307423.
Gendering and Degendering: The Problem of Men’s Victimization in Intimate Partner Relations in Social and Crisis Workers’ Talk
Authors: Venäläinen Satu
Published: June 2021

The notion of intimate partner violence (IPV) as gender-based has been widely questioned by advocates of antifeminist men’s rights movements, who have claimed that societal disregard for men’s victimization in intimate relations is a central component of discrimination against men in contemporary societies. Similar views have been expressed by researchers as part of a gender-neutral discourse articulated in opposition to feminist, or gender-sensitive, understandings of IPV. To date, the views of helping professionals who work with IPV in terms of men’s victimization have been underexplored. This study traces the discursive process of problem construction concerning gender and IPV in social and crisis workers’ (N=21) talk about men’s victimization through focus group interviews conducted in Finland. The analysis shows that social and crisis workers’ sense-making closely aligns with talk about men’s victimization by men’s rights advocates; they construct and justify men’s victimization in intimate relations as a pressing societal concern in ways that both posit gender-specific normative conceptions as a significant, oppressive context for men victims and simultaneously obscure gendered structural inequalities by advocating gender-neutral understandings and solutions for IPV. The analysis highlights challenges in attending to IPV with a gender-sensitive approach in the context of widespread politicization of men’s victimization.
Integrated metabolomics coupled with pattern recognition and pathway analysis to reveal molecular mechanism of cadmium-induced diabetic nephropathy
Authors: Gong Pin , Wang Mengrao , Yang Wenjuan , Chang Xiangna , Wang Lan , Chen Fuxin
Published: June 2021

Diabetic nephropathy (DN) is becoming a worldwide public health problem and its pathophysiological mechanism is not well understood. Emerging evidences indicated that cadmium (Cd), an industrial material but also an environmental toxin, may be involved in the development and progression of diabetes and diabetes-related kidney disease. However, the underlying mechanism is still unclear.

Herein, a DN animal model was constructed by exposing to Cd, the metabolomic profiling of DN mice were obtained by using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), pattern recognition and pathway analysis were performed to screen potential biomarker. Moreover, western blotting was employed to verify the possible mechanism involved in the occurrence of Cd-induced DN.

A total of 66 metabolites in serum have been screened out and identified as biomarkers, including free fatty acids, phospholipids, sphingomyelins, glycerides, and others. Significant differences were demonstrated between the metabolic profiles, including decreased levels of phospholipid and increased content of triglyceride, diacylglycerols, ceramide, lysophosphatidylcholine in Cd-induced DN mice compared with control. Protein expression level of p38 MAPK and Wnt/β-catenin were significantly increased.

UPLC-Q-TOF/MS-based serum metabolomics coupled with pattern recognition methods and pathway analysis provide a powerful approach to identify potential biomarkers and is a new strategy to predict the underlying mechanism of disease caused by environmental toxicant.
Extreme Resistance to Potato Virus A in Potato Cultivar Barbara is Independently Mediated by Ra and Rysto
Authors: Huang Wei , Nie Bihua , Tu Zhen , Li Chunyan , Murphy Agnes , Singh Mathuresh , Song Botao , Zhang Shu , Xie Conghua , Nie Xianzhou
Published: June 2021

Potato virus A (PVA) and potato virus Y (PVY) are two members of genus Potyvirus infecting potato crops worldwide. Host resistance offers an economical and effective means for the control or management of these viruses. In this study, 20 potato clones were screened for their resistance against PVA and PVY by mechanical or graft inoculation assay, and were explored for the relationship between extreme resistance genes Ra and Ry by the detection of molecular markers linked to Ryadg, Rysto, and Rychc. Six clones, including Barbara, Jizhangshu 8, Longshu 7, Longshu 8, M6, and Solara, were found to be extremely resistant to both PVA and PVY; three clones (AC142, Eshu 3, and Shepody) were deemed to be extremely resistant to PVA but susceptible to PVY. To further reveal the inheritance of the extreme resistance (ER) against PVA, a tetraploid F1 population of Barbara × F58050 (susceptible to both PVY and PVA) and a tetraploid BC1 population of BF145 (a PVA-resistant but PVY-susceptible progeny of Barbara × F58050) × F58050 were obtained. Phenotyping of the F1 and BC1 populations by graft inoculation with PVA showed segregation ratios of 3:1 and 1:1 (resistant:susceptible), respectively. These results suggest that two independent loci control ER against PVA in Barbara: one confers ER to both PVA and PVY and the other confers ER to PVA only. The deduced genotype of Barbara is RyryryryRararara.
3D visualization of vertebrate soft tissues using spiceCT (Selectively Perfusable Iodine‐based Contrast‐Enhanced CT) as a rapid alternative to diceCT
Authors: Witmer Lawrence , Porter Wm. Ruger , Cerio Donald , Nassif James , Caggiano Emily G. , Griffin Christine , Ridgely Ryan C.
Published: June 2021

The treatment of vertebrate specimens with radio‐opaque substances to enhance soft‐tissue contrast in CT scans has revolutionized morphological analysis. DiceCT has produced spectacular results and involves immersing specimens in Lugol's iodine. A shortcoming of diceCT is that diffusion (the “d” in “diceCT”) can take days, weeks, or months in large, intact, unskinned specimens. Moreover, long diffusion times can cause marked shrinkage. Alternatively, our team has developed spiceCT, which involves perfusing specimens with Lugol's iodine, yielding excellent results—literally within hours. The vascular system of thawed, unfixed, unskinned specimens (mostly birds and reptiles thus far) is cannulated, and then hypertonic (2.5 or 5%) aqueous Lugol's iodine is injected with a syringe. The solution perfuses well, easily filling capillary beds. Perfusion can be visually monitored in key areas, as well as tactilely via syringe pressure. Staining is rapid, and specimens can be scanned immediately, yielding same‐day results. There is no time for shrinkage, which is a well‐known problem for diceCT specimens immersed in iodine for long periods. The absence of prior fixation shortens processing time and also opens new avenues for final storage in that the specimen can be fixed, refrozen, or even skeletonized. Perfusion rather than diffusion also allows targeting of tissues—selective perfusion (the “sp” of “spiceCT”)—by injecting their vascular supply. One shortcoming of spiceCT is that iodine is too large to cross the blood‐brain barrier (BBB), even in cadaveric specimens. Our team is currently exploring ways to overcome this problem, experimenting with adding EDTA to the Lugol's injection medium to disrupt the cadherins forming the tight junctions of the endothelial cells of the cerebral vasculature. Initial results are promising. SpiceCT is intended to supplement, not replace, diceCT in the toolkit of morphologists.

Support or Funding Information

US National Science Foundation (IOB‐0517257, IOS‐1050154, IOS‐1456503)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dissecting the Mechanisms of Cell Division
Authors: Torres Jorge Z
Published: June 2021

Human cell division is a highly coordinated set of events that ensures the proper transmission of genetic material from one mother cell to two newly formed daughter cells. Key to this process is the proper assembly and functioning of the mitotic microtubule spindle, which relies on a multitude of protein complexes, protein‐protein interactions, and regulatory mechanisms driven by enzymatic activities. Cell division is an essential step in cellular proliferation and misregulation of the cell division machinery can lead to premature sister chromatid separation, chromosomal instability, aneuploidy (a hallmark of many types of cancers) and resistance to cancer therapeutics like antimitotics. Therefore, understanding what the full complement of the cell division machinery is, what their functions are, how they are regulated, and how they cooperate to ensure proper cell division is critical to understanding cell division, tumorigenesis and the response of tumor cells to antimitotic drugs. Here, we present our integrative computational, chemical, proteomic, and genetic approaches to dissect the mechanisms governing cell division and for developing novel cancer therapeutics. We highlight our proteomic approaches to identify novel mitotic microtubule associated proteins with critical roles in cell division and for generating affinity and proximity protein association networks to interrogate their functions. We discuss our efforts to chemically dissect the cell cycle with an emphasis on the discovery of novel cell division inhbitors that can be used to dissect the mechanisms of cell division and for developing new cancer drugs. We are optimistic that our studies will increase our understanding of the mechanisms that ensure proper cell division and how their misregulation can lead to tumorigenesis and chemotherapeutic resistance.

Support or Funding Information

This work was funded by NSF MCB1243645, NIH R01GM117475‐01, ACS 123880‐RSG‐13‐398‐01‐CCG, a Cottrell Scholar Award from the Research Corporation for Science Advancement (RCSA), a V Scholar Award from the V Foundation for Cancer Research and a Basil O'Connor Award from the March of Dimes Foundation.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differential protein splicing of salt‐dependent inteins from Haloquadratum walsbyi
Authors: Lynch Abigeal , Amunya Shirley , Gomez Alvin , Reitter Julie N. , Mills Kenneth
Published: June 2021

Protein splicing is a self‐catalyzed, post‐translational process in which an intervening polypeptide sequence, or an intein, catalyzes its removal from two flanking polypeptide sequences, or exteins, as well as the ligation of the exteins. We are interested in the splicing capabilities of two inteins that interrupt the cdc21 protein from Haloquadratum walsbyi (Hwa). Hwa is a halophilic archaeon found in high salt environments such as the Red Sea. For this reason, we hypothesize that protein splicing may be salt dependent. We are interested in studying the splicing capabilities of both inteins separately and when expressed as part of the same protein. One intein, Cdc21a, does not splice on overexpression in E. coli, but can be induced to splice in vitro on incubation with 2.5 M sodium chloride at 28°. The other intein, Cdc21d, splices in vivo, and can be induced to splice further with higher concentrations of salt. When expressed in the same precursor fusion protein, the inteins continue to show differential activity conditional on salt concentration, leading to alternative spliced products. We hypothesize that this differential protein splicing is due to the folding of the protein under different salt conditions.

Support or Funding Information

This work was supported by the National Science Foundation (grants MCB‐1244089), the Dreyfus Foundation (KVM), and Diane D. Brink P12 to the Alumni/Parent Summer Research Scholarship Fund. AL

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Alpha‐1 adrenergic receptor regulation of seizures and neurodegeneration
Authors: Goldenstein Brianna , Jurgens Chris , Knudson Chris , Lichter Jessica , Carr Patrick , Perez Dianne , Van Doze
Published: June 2021

Neurogenesis has potential as a treatment for epilepsy and neurodegeneration. The endogenous neurotransmitter norepinephrine (NE) may be involved in promoting neurogenesis through the activation of α1 adrenergic receptors (ARs). This project aims to obtain additional evidence for a possible role of α1ARs in neurogenesis and seizures using transgenic mice overexpressing α1AARs or α1BARs or having no functional (knockout) α1AARs or α1BARs. When treated with the epileptogenic agent flurothyl and compared to controls, mice overexpressing α1AARs had more hippocampal interneurons and showed an increase in latency periods preceding seizures while α1BAR overexpressing mice had significantly fewer interneurons and exhibited an enhanced susceptibility to seizures. Electrophysiological recordings during application of an α1AR agonist produced a concentration‐dependent increase in action potential frequency in hippocampal interneurons in normal and α1BAR knockout mice, but not in α1AAR‐knockout mice. These findings are potentially very significant because they link α1AAR‐induced proliferation of interneurons to the antiepileptic actions of NE. Insight into these mechanisms may lead to new treatment strategies for epilepsy and other neurodegenerative diseases. Supported by ND EPSCoR through NSF EPS‐0447679, NSF CAREER 0347259, NIH 5P20RR017699 from the NCRR, and the American Physiological Society.
Structural and functional studies of the Drosophila melanogaster small nuclear RNA activating protein complex (DmSNAPc)
Authors: Stumph William E , Barakat Nermeen H , Lai Hsien‐Tsung
Published: June 2021

The small nuclear RNA activating protein complex (SNAPc) is an evolutionarily conserved multi‐subunit factor required for transcription of the spliceosomal small nuclear RNA (snRNA) genes by both RNA polymerase II (U1, U2, U4, and U5) and RNA polymerase III (U6). Three distinct polypeptides have been identified as subunits of D. melanogaster SNAPc; however, the stoichiometry of these three subunits in DmSNAPc had not been investigated. By co‐expressing each subunit with two different tags and by doing band‐shift and super‐shift analyses, we have determined that DmSNAPc is a heterotrimer with a 1:1:1 subunit stoichiometry. DmSNAPc recognizes an ~21 bp long DNA sequence denoted the PSEA about 40‐60 bp upstream of the transcription start site. Interestingly, the PSEAs of the U1 and U6 genes are not interchangeable even though they are identical at 16 of 21 nucleotide positions. In fact, changing the U1 PSEA to a U6 PSEA inactivated the U1 promoter. We have now found that this substitution does not affect the association of DmSNAPc with the promoter; instead, it disrupts the recruitment of TBP. This finding is consistent with a working model in which DmSNAPc binds in different conformations to the U1 and U6 PSEAs. We believe these conformational differences in DmSNAPc lead to differential RNA polymerase selectivity at the U1 and U6 promoters. Supported by NSF and in part by the California Metabolic Research Foundation.
Green tea extract (GTE) attenuates hepatic injury by reducing oxidative stress and lipid accumulation in ob/ob mice
Authors: Park Hea Jin , Dinatale Dana A. , Chung Min‐Yu , Koo Sung I. , Park Young‐Ki , Lee Ji‐Young , Bruno Richard S.
Published: June 2021

Oxidative stress and excess hepatic lipid are implicated in nonalcoholic fatty liver disease. Based on our previous observation that GTE attenuated hepatic lipid accumulation and injury, we hypothesized that GTE would decrease hepatic oxidative stress. Obese mice (ob/ob, n = 38) were fed a diet containing 0, 0.5 or 1% GTE for 6 wk. Lean mice, as a control, were fed 0% GTE. Serum ALT was 7.3‐times higher (p < 0.05) in obese compared to lean mice and GTE at 0.5 or 1% attenuated it by 25%. Obese mice, compared to lean mice, had greater oxidative stress as suggested by 16% lower hepatic total glutathione (tGSH) and 40% higher malondialdehyde (MDA). tGSH in obese mice fed GTE at 1% was increased to that observed in lean mice. Hepatic MDA in obese mice fed GTE at 0.5 or 1% was 16‐22% lower (p < 0.05) than in obese controls. Obese mice had 2.3‐times greater (p < 0.05) hepatic total lipid (TL) compared to lean mice which was lowered by 13% in obese mice fed GTE at 1%. This effect was consistent with hepatic triglyceride (TG) and total cholesterol (TC). Alterations in lipogenic gene expression may be involved in the hepatic lipid lowering effect of GTE. ALT was correlated (p < 0.05) to tGSH (r = ‐0.339) and MDA (r = 0.358), as well as TL (r = 0.895), TG (r = 0.777) and TC (r = 0.634). The data suggest that GTE attenuates hepatic injury by inhibiting lipid accumulation and decreasing oxidative stress. Supported by USDA NRI (2007‐02303) to RSB.
The onset and magnitude of cardiovascular drift depend on exercise intensity in recreational runners.
Authors: Winger Jena , Murphy Kristi , Stavrianeas Stasinos
Published: June 2021

PURPOSE

To examine the potential effects of cardiovascular drift (CVD) on aerobic and anaerobic metabolism.

METHOD

Recreational runners (n=10, age 40.3±8.3years, height 176±7cm, weight 71.29±10.76kg, VO2max 57.29±5.96ml▸kg−1▸min−1) participated and each performed 5 running tests 2‐4 days apart: a VO2max test (2‐min stages to exhaustion), a Maximal Lactate Steady State test (MLSS), and 3 prolonged (45 min) submaximal bouts at intensities corresponding to 95%, 100%, and 105% of the MLSS velocity (1% grade). HR and VO2 were recorded continuously; blood lactate was measured after each stage during the first 2 tests, and every 10 minutes for the 3 prolonged bouts.

RESULTS

Onset of CVD was different for every participant, often with no HR plateau in the 105% MLSS bout. Small differences in exercise intensity (0.22 m▸sec−1) yielded significant differences (p < 0.05) across the 3 intensities in the amplitude of CVD (increases of 7 BPM, 14 BPM, and 18 BPM for the 95%, 100%, and 105%), VO2 (1.42 ml▸kg−1▸min−1, 1.8 ml▸kg−1▸min−1, and 1.39 ml▸kg−1▸min−1), and blood lactate (0.25 mmol▸L−1, 0.88 mmol▸L−1, and 1.08 mmol▸L−1) between steady state and minute 40.

CONCLUSION

We successfully measured changes associated with the metabolic cost of exercise during CVD. The onset of CVD is affected by the intensity of exercise and the amplitude of CVD is greater as exercise intensity increases.

Supported by the Mary Stuart Rogers Foundation and an NSF grant (DUE 0511219).
Dgrip79 resembles g‐tubulin interacting proteins but serves distinct functions
Authors: Zahm Christopher , Riederer Allison , Son Sona , Weise Christiane
Published: June 2021

The centrosome plays a crucial role in the faithful transmission of chromosomes during cell division and serves as a nucleator and organizer of the microtubules that make up the mitotic spindle. Despite its indispensable function many aspects of centrosome biology remain unknown. An essential component of the centrosome is γ‐tubulin, which is required for microtubule nucleation. The Drosophila melanogaster γ‐tubulin interacts with at least five additional proteins (Grips) to form a 'γ‐tubulin ring complex' (γTuRC). The grips are related to one another by the presence of one or two regions of homology named 'grip motifs'. Grip motifs are rare: only seven grip‐containing proteins exist in the Drosophila genome. Because five of these are components of the γTuRC, it is possible that the grip motifs are somehow involved in γTuRC and/or centrosome function. To gain a better understanding of the function of the grip motif, we have begun to analyze the cell biology of Dgrip79, a 79kDa protein that contains both grip motifs. We show that Dgrip79 is expressed only in testes. In developing sperm, Dgrip79 localizes along the long axis of the nucleus, most likely associating with a bundle of microtubules of unknown function that runs along the length of the sperm head. Sucorse gradient analysis confirms that Dgrip79 is unlikely to be a part of the gTuRC. Together, our data suggest that Dgrip79 may be a microtubule binding protein involved in spermatogenesis.

Grant Funding Source

NSF
Fiber consumption and metabolic syndrome in adults: Results from NHANES 1999‐2004
Authors: O'Neil Carol , Nicklas Theresa , Zanovec M , Cho Susan
Published: June 2021

The objective of this study was to examine the effect of increasing fiber and whole grain (WG) consumption on the odds of having metabolic syndrome (MetS) in a recent, nationally representative sample of US adults 19 to 51 years (n=7,039) and 51+ years (n=6,237) using a secondary analysis of NHANES 1999‐2004 data. . Participants were divided into four fiber consumption groups: <10g/d, 10 to <15, 15to <20, =20g/day. For a separate analysis of WG, participants were also divided into four WG consumption groups: <0.6 (control), 0.6 to <1.5, 1.5 to <3.0 and = 3.0 servings. MetS was defined using the ATPIII definition. Least‐square means + SE were calculated. For adults 19‐50 years, mean fiber intake was 14.97 g + 0.37; ORs with MetS were: 0.958 (CI = 0.755 to 1.216), 0.800 (CI = 0.603 to 1.063), and 0.807 (CI = 0.608 to 1.072) for the three fiber groups, respectively; p for trend with MetS was 0.08. For adults 51+ years, mean fiber intake was 15.65 g + 0.26; ORs with MetS were: 1.31 (CI = 1.05 to 1.64), 0.89 (CI = 0.71 to 1.14), and 0.60 (1.47 to 0.77) for the three WG groups, respectively; p for trend was 0.0010. However, whole grain intake was not associated with reduced ORs of MeS in both age groups. These data suggest that fiber consumption may have a positive impact on MeS. Supported by USDA & Kellogg's Corporate Citizenship Fund.
Cooking schools improve food intake patterns and diabetes knowledge of people with diabetes
Authors: Archuleta Martha , VanLeeuwen Dawn , Halderson Karen , Jackson K'Dawn , Bock Margaret Ann , Eastman Wanda , Powell Jennifer , Titone Michelle , Wells Linda
Published: June 2021

Implementation of nutrition recommendations is often difficult for people with diabetes. The objective was to determine if cooking schools delivered by the Cooperative Extension Service in collaboration with registered dietitians and certified diabetes educators improved dietary patterns and knowledge of people with diabetes. The research design was quasi‐experimental with a pretest, posttest design. Each subject served as his or her own control. Kitchen Creations cooking schools intervention consisted of four, three‐hour long lessons. The cooking schools featured current nutrition recommendations for people with diabetes and hands‐on food preparation and cooking experiences. Participants completed three‐day food records and demographics and knowledge questionnaires prior to attending Kitchen Creations and one month after completing the Kitchen Creations series. Following participation in Kitchen Creations, participants showed significant (p<0.05) decreases in energy, fat energy, fat grams, percent of calories from fat, fat exchanges, saturated fat energy, saturated fat grams, carbohydrate grams, cholesterol (mg) and sodium (mg). Bread exchanges and "other carbohydrate" exchanges decreased (p<0.05.) Vegetable exhanges increased in women (p<0.05) but not in men. Knowledge of nutrition recommendations for people with diabetes significantly (p<0.05) improved. Results indicate that a cooking school approach can successfully change food intake patterns. Funding provided by the USDA Cooperative State Research, Education & Extension Service, New Mexico State University and the New Mexico Department of Health, Diabetes Prevention and Control Program.
Decreased blood volume does not contribute to impaired hemodynamic counterregulation to hemorrhagic shock in acute alcohol intoxicated rodents
Authors: Whitaker Annie McGraw , Molina Patricia E
Published: June 2021

Acute alcohol intoxication (AAI) accentuates hypotension (HT) and impairs blood pressure recovery during fluid resuscitation following hemorrhage (HEM). We hypothesized that AAI may decrease blood volume (BV) and thus contribute to the greater HT in response to a given blood loss. The aim of this study was to determine whether AAI decreases BV. Chronically‐catheterized, adult male Sprague‐Dawley rats (250‐300g) received a primed‐constant (2.5g/kg + 300mg/kg/h) 15h intragastric infusion of alcohol, dextrose (DEX), or no infusion (NI). AAI resulted in a marked increase in urine output 1 hr and 2h into the infusion as compared to DEX‐infused and NI controls, (72% and 84% respectively; p<0.050) and a significant decrease in urine osmolarity (OSM) (58%, p<0.050). At the completion of the 15h infusion, there were no differences in urine output or OSM among the groups. AAI produced a significant (4%; p<0.05) increase in plasma OSM 2h into the infusion, which normalized at 15h of alcohol infusion. BV (10%) was not significantly different between groups. These results show that AAI produces early stimulation of urine output associated with increased plasma OSM. We hypothesize that this results in increased vasopressin release which increases water reabsorption, preserving BV. These findings suggest that the greater HT following HEM is not the result of decreased BV. Supported by DOD PR‐054196 and NIAAA‐AA7577.
FATTY ACIDS MODULATE TOLL‐LIKE RECEPTOR 4 ACTIVATION THROUGH REGULATION OF RECEPTOR DIMERIZATION AND RECRUITMENT INTO LIPID RAFTS IN A ROS DEPENDENT MANNER
Authors: Wong Scott , Kwon Myung‐Ja , Snodgrass Ryan , Choi Augustine M.K. , Kim Hong‐Pyo , Nakahira Kiichi , Hwang Daniel
Published: June 2021

Results from our previous studies revealed that saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4. However, the underlying mechanism has not been understood. The saturated fatty acid lauric acid (C12) induces dimerization and recruitment of TLR4 into lipid rafts, and enhanced the association of TLR4 with MD‐2 and downstream adaptor molecules leading to target gene expression. However, docosahexaenoic acid (DHA) inhibited LPS‐ or C12‐induced dimerization and recruitment of TLR4 into lipid rafts. Dimerization of TLR4 induced by C12 was accompanied by activation of NADPH oxidase (NOX) and reactive oxygen species (ROS) generation. An inhibitor of NOX suppressed C12‐induced dimerization of TLR4. Together, these results demonstrate that C12 and DHA reciprocally modulate TLR4 activation by regulation of the dimerization and recruitment of TLR4 into lipid rafts, which are coupled events mediated at least in part by NOX‐dependent ROS generation. These results provide a new insight in understanding the mechanism by which fatty acids differentially modulate TLR4‐mediated signaling pathway and consequent inflammatory responses which are implicated in the development and progression of many chronic diseases (supported by DK064007 from NIH, 2001‐35200‐10721 from USDA and program funds from the Western Human Nutrition Research Center/ARS/USDA).
A nutrition and physical activity intervention using smart phones in physical education classes at a junior high school
Authors: Mosqueda Martha I , Martinez Cathy L , Orr Barron J , Merchant Nirav C , Going Scott B , Hongu Nobuko
Published: June 2021

The purpose of this study was to implement smart phone based nutrition and physical activity (NPA) as part of a physical education class at a junior high school in Pinal County, Arizona, where over 70% of enrolled students are participating in free or reduced meals program. Four interactive activities (Treasure Hunt, Mapping, Earth Drawing, and Tag) that included nutrition information were implemented using a social networking and smart phone with multi‐featured mapping (global positioning system and digital photography). Daily NPA factoids were delivered to participants using automated message delivery applications developed by the University of Arizona Stealth Health Project team. Weight and height were measured, and food behavior and physical activity were assessed in 30 participants in a pre and post intervention. 9 females and 21 males (mean ± SD; age 12.9 ± 0.7 years, weight 47.7 ± 9.2 kg, height 159 ± 7.9 cm, BMI 18.76 ± 2.4 kg/m2) participated in the 8‐weeks study. Before each interactive activity participants were asked to wear a pedometer (Yamax Digi‐Walker, SW200). After each activity a feedback survey was answered and total steps were recorded. Preliminary data suggests that smart phone‐based NPA interventions have a potential to enhance physical activity and healthy eating habits in adolescents.

Supported by USDA, NIFA, Human Nutrition and Obesity Program and American Dietetic Association Foundation

Grant Funding Source : USDA
Peer led behavioral intervention and changes in weight status in female college freshman
Authors: Evans Ellen M , Schmidt Michael D. , Mojtahedi Mina C. , Guest Dolores D. , Das Bhibha M. , Mailey Emily L.
Published: June 2021

Weight gain is common during the first year of college and interventions to attenuate weight gain have had equivocal results. The study aim was to assess the effectiveness of a peer‐delivered, self‐efficacy based, weight management intervention in female freshman (n=257; 18.0±0.3 y; 73.5% White) in a university setting. Participants were randomized to an intervention group (PEER) or control group (CON) and were assessed for body weight (WT), body mass index (BMI), and waist circumference (WC). At baseline, 75.5% of the sample was normal weight (62.3±9.6 kg, BMI 23.0±3.1 kg/m2, WC 82.3±8.3 cm). Adjusting for baseline measures, changes over the academic year were not significantly different between PEER and CON for WT (1.4±2.5 vs. 1.6±3.1 kg, p=0.61), BMI (0.49±0.96 vs. 0.54±1.14 kg/m2, p=0.72), or WC (0.07±4.19 vs. 1.11±4.80 cm, p=0.07). However, weight status change among the total sample was highly variable with 27.3% increasing WT by >=5% and 23.4% increasing WC by >=5% over the academic year with no difference between PEER and CON (25.8% vs. 28.8%, p=0.60; 19.2% vs. 27.7%, p=0.12, respectively). Weight gain may be a health issue for some female freshman transitioning to college. More research is needed to determine effective and sustainable intervention with appropriate dose‐response to elicit behavior change in this increasing at‐risk population for weight management.

Grant Support: USDA 2008‐55215‐18825
Neonatal and maternal iron status, but not serum folate, is related to placental expression of the proton coupled folate transporter (PCFT)
Authors: Cao Chang , Bemis Thomas , Young Melissa , McNanley Thomas , Cooper Elizabeth , Pressman Eva , Westerman Mark , Guillet Ronnie , O'Brien Kimberly
Published: June 2021

The proton coupled folate transporter (PCFT) has been identified as a major tissue folate transporter but this protein also exhibits a low‐affinity for heme iron (Fe). This study aimed to characterize placental PCFT expression in relation to maternal and neonatal folate and Fe status in 104 pregnant adolescents (ages 13–18y) enrolled in a prospective study examining effects of maternal nutrition on neonatal health. Fe status indicators (hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), total body Fe) were assessed at mid‐gestation (wks 23.4±3.4), delivery (wks 39.9±1.3) and in cord blood. Expression of PCFT, heme oxygenase (HO)‐1 and HO‐2 were assessed by Western blot in placental tissue collected at delivery. Placental PCFT was associated with neonatal sTfR (p=0.01, n=91, R2=0.07) and hepcidin (p=0.04, n=83, R2=0.05). Significant relationships were found between expression of PCFT with HO‐1 (p=0.009, n=55, R2=0.12) and HO‐ 2 (p=0.006, n=50, R2=0.15). Adolescents with depleted Fe stores (SF<12μg/L) at delivery had elevated PCFT expression compared to Fe sufficient adolescents (p=0.03, n=91). Placental PCFT was not related to folate levels in maternal mid‐gestation sera or in cord sera. A multivariate model that included neonatal sTfR and placental HO‐1 explained 20% variation in placental PCFT (n=48, p=0.0027). Placental PCFT expression was related to neonatal and maternal Fe status and placental HO‐1 expression, suggesting an involvement of PCFT in placental Fe utilization and transport. The lack of relationship of PCFT with maternal and cord serum folate suggests a folate‐independent regulation of PCFT expression in the human placenta. Funded by USDA: 2005‐35200 & 2008‐0857

Grant Funding Source : USDA
Food Safety Knowledge, Attitudes, Behaviors and Intended Behaviors of Middle Schoolers
Authors: Quick Virginia , Corda Kirsten , Byrd-Bredbenner Carol
Published: June 2021

Little attention has been given to pre‐ and early‐teens’ understanding of safe food handling, despite their interests in studying food safety (FS) and preparing food, growing responsibilities related to family food shopping and preparation, and future adulthood roles as caregivers. The purpose of this study was to explore middle schoolers’ food safety cognitions using an online survey developed based on Health Belief Model and Theory of Reasoned Action constructs. Findings indicate that overall FS knowledge of middle schoolers from two states (n=207; 57% boys) was inadequate (mean score=57% correct), with males and females scoring similarly. Only 43% and 67% of participants reported always washing their hands before making a snack and washing fruits and vegetables before eating them, respectively. Just one‐third of participants agreed they were susceptible to food poisoning, yet 83% agreed they had an interest in learning about FS. Independent t‐tests revealed that girls had significantly (p<0.05) stronger attitudes towards the importance of FS and sanitation, greater FS self‐efficacy, and stronger intentions to perform FS behaviors. These findings suggest a need for middle school FS education. Funding: USDA, National Food Safety Initiative
Contribution of school lunches to USDA Food Patterns: findings from the fourth School Nutrition Dietary Assessment Study (SNDA‐IV)
Authors: Crepinsek Mary Kay , Condon Elizabeth , Fox Mary Kay , Hirschman Jay
Published: June 2021

The National School Lunch Program (NSLP) serves lunches to 32 million children on an average school day. An ongoing goal of the program is to better align school meals with dietary practices recommended in the Dietary Guidelines for Americans. The USDA Food Patterns translate the 2010 Dietary Guidelines into daily amounts of nutrient‐dense foods to eat from five food groups and their subgroups, as well as healthy amounts of oils and limits on calories from solid fats and added sugars (SoFAS). One objective of SNDA‐IV was to assess for the first time the potential contribution of school meals to daily food intakes recommended in USDA's Food Patterns. Between January and June 2010, school foodservice managers in a national sample of schools completed a detailed menu survey for one week. Food items reported were linked to the MyPyramid Equivalents Database and average amounts of Food Pattern food groups available in NSLP lunches were compared with recommendations for school‐age children. On average, lunches offered one‐third or more of recommended amounts of fruit, grains, dairy foods, and oils but were low in whole grains and high in calories from SoFAS. Leading sources of SoFAS calories included flavored milk, baked desserts, and pizza/pizza products. These findings provide an important baseline against which recent regulatory changes in the NSLP can be assessed. Research supported by the USDA, Food and Nutrition Service.
Induction of VEGF expression in monocytes by alpha‐tocopherol and alpha‐tocopheryl phosphate via PI3Kgamma/Akt and hTAP1/SEC14L2‐mediated lipid exchange (1000.1)
Authors: Zingg Jean‐Marc , Azzi Angelo , Meydani Mohsen
Published: June 2021

In several studies, vitamin E has been observed to influence angiogenesis and vasculogenesis. We recently observed that the phosphorylated form of α‐tocopherol (αT), α‐tocopheryl phosphate (αTP), increases the expression of the vascular endothelial growth factor (VEGF), which may stimulate angiogenesis and vasculogenesis and enhance the survival of cells. Here we investigated the molecular signaling mechanisms by which αTP induces VEGF expression using cultured THP‐1 monocytes and HEK293 cells as model systems. αT and more so αTP increased VEGF‐promoter activity in a phosphatidylinositol‐3‐kinase gamma (PI3Kγ) ‐dependent manner. In contrast, after over‐expression of PI3Kγ and/or Akt, VEGF promoter activity is inhibited by αT and more so by αTP. PI3Kγ‐induced VEGF expression was reduced when the human tocopherol associated protein 1 (hTAP1/SEC14L2) was over‐expressed, that could be reverted by αT and more so by αTP. Recombinant hTAP1/hSEC14L2 binds both αT and αTP and reduces the in vitro activity of the PI3Kγ most likely by forming a stalled/inactive hTAP1/PI3Kγ heterodimer. The addition αT, βT, γT, δT or αTP differentially stimulates PI3Kγ. We suggest a novel signaling mechanism by which αT or αTP stimulate PI3Kγ activity by facilitating egress and presentation of sequestered PI from hTAP1 to the enzyme and/or dissociating the inactive heterodimer. Supported by USDA Contract #58‐1950‐0‐014.

Grant Funding Source: Supported by USDA Contract #58‐1950‐0‐014
Identification and characterization of fatty acid alkyl esterases found in Staphylococcus aureus (1002.3)
Authors: Saylor Benjamin , Love John
Published: June 2021

Identification and Characterization of Fatty Acid Alkyl Esterases Found in Staphylococcus aureus Alternative energy is a major field of current research. Biodiesel, a mixture of fatty acid alkyl esters, is the most versatile biofuel in current use. This is due to the fact that it is similar enough to gasoline that it is compatible with the diesel engines found throughout the existing global infrastructure. Biodiesel precursor lipids are abundant in cultivated feedstock organisms such as algae and bacteria. However, the standard process for converting oil to biodiesel is heat‐intensive and requires complete removal of water, greatly reducing the net energy gained in its manufacture. Our work constitutes an attempt to explore enzymatic synthesis of biodiesel with lipids like those derived from emerging fuel crops.

Previous literature describes fatty acid alkyl ester formation in Staphylococcal lesions, formed by partially characterized esterase activity from an unidentified source. We have identified the enzymes responsible for this activity by using a combination of size exclusion chromatography, gas chromatography‐mass spectrometry, and mass spectrometric protein sequencing. These two highly similar enzymes in the glycerol ester hydrolase (geh) family of proteins catalyze the synthesis of fatty acid alkyl esters in aqueous conditions at or near room temperature. We have demonstrated that other, similar lipases do not exhibit this behavior. We have expressed one of these Staphylococcal esterases in E. coli, and shown via gas chromatography that the expressed protein catalyzes the formation of fatty acid alkyl esters. Based on sequence similarity to homologous proteins that have already been crystallized, we have predicted a structure for these enzymes and intend to engineer mutants with higher rates of catalysis.

Grant Funding Source: NSF
Low‐abundance plasma protein differences between African‐American and Caucasian early pubertal females following supplementation with 9 mg Zn (1043.10)
Authors: Grider Arthur , Lewis Richard , Laing Emma , Wickwire Kathie
Published: June 2021

The purpose of this research was to determine whether supplementation with oral zinc levels near the RDA for 4 wks would affect plasma protein levels in African‐American (AA) and Caucasian (C) early pubertal females. The subjects were given either 9 mg elemental zinc (n=75; 40 C, 35 AA) or placebo (n=71; 40 C, 31 AA) to consume for 4 wks. Plasma was collected from subjects at baseline (BL) and 4 wks, and was analyzed for zinc by atomic absorption. Plasma from subjects that were most responsive to zinc supplementation (BL to 4wk; n=5), or exhibited the least difference between BL and 4wk (placebo; n=5) were analyzed. Individual plasma samples were prefractionated on immunoaffinity columns to remove 14 high‐abundant plasma proteins. Effluent proteins were separated by two‐dimensional gel electrophoresis (400 µg; 15% acrylamide 2nd dimension). The gels were stained with Coomassie blue G‐250 and analyzed by densitometry. Significant differences were determined by Student’s t‐test. Comparisons were made between untreated (UnTrt; n=15) vs. zinc‐treated (ZnTrt; n=5) plasma. Two proteins were affected by zinc consumption, 33.8kDa/pI 5.4 (UnTrt C: 0.70±0.11 (SEM), ZnTrt C: 1.56±0.46 (SEM; p=0.02); UnTrt AA: 0.73±0.10 (SEM), ZnTrt AA: 0.64±0.24 (SEM; p=0.67) and 32.4kDA/pI 5.8 (UnTrt C: 1.14±0.22 (SEM), ZnTrt C: 1.58±0.18 (SEM; p=0.16); UnTrt AA: 1.97±0.22(SEM), ZnTrt AA: 1.02±0.28 (SEM; p=0.03). These zinc‐responsive proteins were affected by the race of the supplemented individuals, suggesting there are subtle differences in the zinc metabolism of individuals from different racial or cultural backgrounds.

Grant Funding Source: Supported by USDA Hatch GEO00682
Urinary proanthocyanidin A2 as a biomarker of consumption of cranberry juice ő a pilot study (1044.3)
Authors: Chen C‐Y. , Zampariello Carly , Blumberg Jeffrey
Published: June 2021

The absence of a validated biomarker of cranberry intake has limited the ability to interpret results from many human studies, particularly long‐term clinical trials examining the effect of cranberries on health outcomes. Cranberries are rich in type A proanthocyanins, a flavonoid found in very few other foods. The objective of this study was to determine whether proanthocyanin dimer A2 (PAC‐A2) could be a useful biomarker of cranberry intake. Five healthy, premenopausal women were asked to consume 237 mL/d cranberry beverage containing 140 mg PAC, according to a weekly dosing schedule of 0 to 7 times daily over a 7 wk period. Eleven 24‐h and morning spot urine samples each were collected for PAC‐A2 analysis. Urine samples were treated with β‐glucuronidase and extracted with ethyl acetate. The ethyl acetate fraction was dried under N2 gas, reconstituted in a NH4HCO2 buffer, and extracted with an activated solid phase Bond Elut PBA cartridge. PAC‐A2 was separated by a Kinetex C18 column (4.6 x 150 mm x 2.6 µm) and quantified by LC‐MS/MS operating in negative ion mode. The variation in response of PAC‐A2 spiked to 11 urine samples collected from non‐study volunteers was 4.8%. The assay limit of quantification for urinary PAC‐A2 is 0.25 ng/mL. Results from this pilot study suggest that PAC‐A2 is not excreted in the urine in a frequency‐dependent manner corresponding with intake. Funded by the Cranberry Institute and USDA.

Grant Funding Source: Supported by Cranberry Institute and USDA
Role of WWOX and NF‐κB in lung cancer progression (1049.2)
Authors: Chang Nan‐Shan
Published: June 2021

The pro‐inflammatory, pro‐survival transcription factor NF‐κB is considered as a tumor promoter. Tumor necrosis factor alpha (TNF‐α or TNF) mediates NF‐κB activation. Tumor suppressor WWOX (FOR or WOX1) is a downstream effector of the TNF signaling. Thus, activation of both WWOX (FOR or WOX1) and NF‐κB may occur during TNF signaling and/or under stress conditions. Indeed, the first WW domain of WWOX induces the activation of NF‐κB‐responsive promoter without TNF participation. It appears that WWOX counteracts with NF‐κB in regulating cell survival and death. For example, WWOX becomes activated with Tyr33 phosphorylation and relocates together with NF‐κB and many transcription factors to the nucleus to cause neuronal death in sciatic nerve‐transected rats. While WWOX is frequently lost in lung cancer and many other cancers, NF‐κB activation‐induced cancer promotion probably requires WWOX‐independent signaling networks to induce expression of pro‐survival factors. The antagonistic role of WWOX and NF‐κB in the regulation of lung cancer progression is discussed.

Grant Funding Source: NSC and NHRI, Taiwan, and DoD, USA
Efficacy of a novel integrin‐targeted anti‐c‐Myc nanotherapy against multiple myeloma in mice (1054.11)
Authors: Soodgupta Deepti , Pan Dipanjan , Hu Grace , Sen Pan Angana , Yang XiaoXia , Prochownik Edward , Lanza Gregory , Tomasson Michael
Published: June 2021

The MYC oncoprotein drives multiple myeloma (MM) pathogenesis, but the utility of small molecule inhibitors of MYC‐MAX dimerization is limited by poor efficacy. We first sought to test the efficacy of a novel MYC‐MAX dimerization inhibitor prodrug. Treatment of three MM cell lines (mouse and human) with a lipase‐labile prodrug inhibitor of MYC‐MAX dimerization (MI1‐PD) decreased cell viability more than parent drug MI1 on an equimolar basis and increased apoptosis. However, MI1‐PD is hydrophobic, limiting translation to in vivo use. To overcome this challenge, we next determined if the efficacy of MI1‐PD could be improved by delivery in nanoparticles targeted to MM‐specific integrins. Integrin‐targeted, MI1‐PD‐containing nanoparticles inhibited growth and induced apoptosis compared to control nanoparticles without drug, or without integrin‐targeting. Binding and efficacy of nanoparticles correlated with integrin expression in target cells. A mouse model of MM was used to assess in vivo efficacy of nanoparticle‐bound MI1‐PD, with survival used as the primary endpoint. In vivo, administration of nanoparticle‐bound MI1‐PD conferred significant survival benefit versus untreated controls (52 days vs. 29 days, p=0.001). Our results suggest the feasibility of an improved integrin‐targeted nanotherapy approach to disrupt MYC‐MAX dimerization using a lipase‐labile prodrug.

Grant Funding Source: This work was supported by the Department of Defense Grant Award # W81XWH1110446