bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary phenolic compounds modify glutathione redox homeostasis and cytokine release in human T lymphocytes (134.1)
Authors: Richardson Sian , Ford Christopher , Crozier Alan , Lotito Silvina , McArdle Francis , McArdle Anne , Jackson Malcolm 
Published: June 2021

Polyphenols and phenolic acids are abundant in fruits and vegetables. Twenty‐nine dietary phenolic compounds were screened for effects on cytokine release (interleukin 2 (IL2), interleukin 8 (IL8), and tumour necrosis factor α (TNFα)) by Jurkat T‐lymphocytes. Cells were treated with phenolic compounds for 48h, with or without stimulation with 25ng/ml phorbol myristate acetate and 5μg/ml phytohaemagglutinin (PMA/PHA) to induce cytokine release at the 24h time point.Polyphenols had more anti‐inflammatory effects than phenolic acids. In unstimulated cells, 1μM resveratrol decreased IL2 by 42±7% and IL8 by 32±8%, compared with vehicle controls (p<0.05). For PMA/PHA stimulated cells, 1μM isorhamnetin reduced IL2 by 50±4%, IL8 by 58±6% and TNFα by 63±7%, and curcumin reduced IL2 by 43±14%, IL8 by 30±7% and TNFα by 22±5 (p<0.05). Compounds that significantly modulated cytokine release were investigated for effects on glutathione redox status. Cells treated with 1µM epigallocatechin gallate (EGCG) or pyrogallol increased total and reduced glutathione compared with vehicle controls and reduced glutathione redox potentials from ‐211±3mV (controls) to ‐216±2mV (EGCG) and ‐221±2mV (pyrogallol; p<0.05). Polyphenols demonstrating anti‐inflammatory and redox modulating effects will be further investigated using proteomics to identify cellular pathways responsive to treatments with polyphenols.Grant Funding Source: Supported by BBSRC DRINC and Unilever
Plasma folate levels are inversely associated with natural killer cell degranulation in mice (135.1)
Authors: Warzyszynska Joanna , Sohn Kyoung‐Jin , Spring Christopher , Duan Angela , Kim Sung‐Eun , Carlyle James , Kim Young‐In 
Published: June 2021

High intake and plasma levels of folic acid (FA), the synthetic form of the B‐vitamin folate, were associated with reduced natural killer (NK) cell cytotoxicity in post‐menopausal women. This observation has not yet been confirmed. Thus, we examined the relationship between dietary FA intake/plasma folate levels and NK cell activity in an animal model. Post‐weaning C57BL/6 mice were randomized to receive diets containing 2 (control) or 20 mg FA/kg diet for 3 months. A flow cytometry based CD107a and IFN‐γ detection assay was used to assess splenic NK cell activity. Plasma folate levels were significantly higher (p < 0.0001) in the high FA group. Plasma folate levels were significantly and inversely associated with the frequency of NK cell degranulation (%CD107a+ NK cells) in response to stimulation with the mouse T‐cell lymphoma YAC‐1 and cytokines (rs = ‐0.520; p = 0.035) but not in response to mitogenic stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. Plasma folate levels were not associated with IFN‐γ production (%IFN‐γ+ NK cells) in response to either YAC‐1 and cytokine or PMA/ionomycin stimulation. Our findings corroborate an inverse association between high FA levels and NK cell cytotoxicity and suggest that reduced target cell recognition, evidenced by reduced degranulation in response to cancer cell targets but not in response to mitogenic stimulation, is a likely mechanism behind this inverse association. Our data suggest that impaired NK cell function may be a mechanism behind the purported tumor‐promoting effect associated with high FA supplementation.Grant Funding Source: Supported by CIHR MOP #14126
Regulation of the protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs (137.1)
Authors: Suryawan Agus , Nguyen Hanh , Parada Rosemarie , Davis Teresa 
Published: June 2021

The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin (Ins) and amino acids (AA), especially leucine (leu), modulate protein synthesis in skeletal muscle and how this changes with development. These studies aimed to determine whether Ins, AA or Leu alter the abundance and activation of ubiquitin‐proteasome, i.e., atrogin‐1 (MAFbx) and muscle RING‐finger protein‐1 (MuRF1), and autophagy‐lysosome, i.e., microtubule‐associated protein light chain 3 (LC3) and lysosomal‐associated membrane protein 2 (Lamp‐2), protein degradation systems and whether the responses change with age. In study 1, overnight fasted 6‐ and 26‐d‐old pigs were infused with saline or with insulin or AA to achieve fed levels. In study 2, overnight fasted 6‐d‐old pigs were infused with Leu while Ins and AA were kept at fasting levels. Abundance of atrogin‐1, but not MuRF1, was greater in 26‐ than in 6‐day‐old pigs (P<0.05) and was not affected by Ins, AA, or Leu. Abundance of LC3 was higher in younger pigs and not affected by treatment (P<0.05). LC3‐II/LC3‐I ratio was reduced by Ins, AA, and Leu (P<0.05). This response was more profound in younger pigs. Abundance of Lamp‐2 was not affected by treatment or development. In conclusion, Ins, AA, and, in particular, Leu act as signals to modulate muscle protein degradation in neonates.Grant Funding Source: Supported by NIH AR444474 and USDA/ARS 6250‐51000‐055
Tissue resident macrophages regulate IL‐23‐dependent granulopoiesis (146.7)
Authors: Mackey Lantz , Perez Eliezer , Rose Jason , Homeister Jonathon 
Published: June 2021

Mice deficient in α(1,3)‐fucosyltransferases 4 and 7 (FUT‐/‐) lack selectin ligand activity and selectin‐dependent leukocyte trafficking, resulting in altered IL‐23‐dependent granulopoiesis. It is not clear if this granulopoiesis is regulated by bone marrow‐derived macrophages (BMMC) or a distinct population of tissue resident macrophages (TRM). We hypothesized that the loss of FUT‐dependent trafficking reduces the number of neutrophils able to infiltrate tissues, undergo apoptosis, and be phagocytosed by TRMs, altering IL‐23 production. Primary Kupffer cells (pKC) and BMMC were isolated from FUT‐/‐ and WT mice, stimulated in vitro with LPS, and assessed for IL‐23 production. WT mice were irradiated and their hematopoietic system was reconstituted with 1x106 bone marrow cells isolated from WT or FUT‐/‐ mice. Six weeks after reconstitution, circulating WBC counts were assessed. There was no difference in gene expression levels of IL‐23 between WT and FUT‐/‐ pKCs or BMMCs, indicating that IL‐23 production from FUT‐/‐ macrophages is intact. WT mice reconstituted with FUT‐/‐ bone marrow show a pronounced neutrophilia similar to that seen in FUT‐/‐ mice. These results confirm that FUT‐dependent neutrophil trafficking is required for the regulation of granulopoiesis and suggest that the TRM populations are responsible for clearing apoptotic neutrophils and regulating IL‐23 production in granulopoiesis.Grant Funding Source: R01‐HL090823, T32‐HL069768
Micromechanical forces regulate vascular patterning in the chick chorioallantoic membrane (15.3)
Authors: Belle Janeil , Ysasi Alexandra , Bennett Robert , Ackermann Maximilian , Wagner Willi , Konerding Moritz , Tsuda Akira , Mentzer Steven 
Published: June 2021

Mechanical forces have been implicated in blood vessel growth associated with diverse activities such as organ development and wound healing; however, the link between mechanical forces and network structure remains elusive. To test the hypothesis of a direct effect of mechanical force on axial blood vessel growth, we studied ex ovo chick embryo chorioallanotic membranes (CAMs) between embryonic development days 10 to 13. Uniaxial stretch was applied to CAMs for 72 hours using computer‐controlled servomotors to provide a reproducible stretch field. Sholl analysis of fluorescent micrographs of CAM vasculature and scanning electron microscopy (SEM) of vascular corrosion casts were used to characterize vascular structure. Distinct vessel branching was observed across the stretch field and among stretch and control CAMs. Vessel bifurcation angles were significantly lower in stretched CAMs (30.8°; 69.2°, p< 0.01). Mean interbranch length was longer in stretched compared to control CAMs (2.63 mm ± 0.58; 0.93 mm ± 0.33, p< 0.01). Corrosion casting and SEM demonstrated marked sprouting and intussusceptive angiogenesis in the capillary plexus in stretched areas of CAM. Mechanical stretch in the CAM may stimulate axial growth of conducting vessels and both sprouting and intussusceptive angiogenesis in gas exchange capillaries. These results indicate that mechanical force may have vessel‐specific influences on vascular patterning.Grant Funding Source: Supported by NIH 5T32‐CA009535
Estradiol activates AMPK through interaction with extrogen receptor beta (15.4)
Authors: Lipovka Yulia , Konhilas John P. 
Published: June 2021

The susceptibility and progression of cardiovascular disease (CVD) increases in post‐menopausal women. AMP‐kinase (AMPK) has emerged as prominent player as a cellular energetic regulator that is known to modify both metabolic and contractile function in the heart. Our on‐going studies indicate that AMPK activation is down‐regulated during menopause and that this may play a role in the increased risk of CVD in post‐menopausal women. The aim of this study is to determine the mechanistic link between estrogen (Estradiol) and AMPK activation. We show that Estradiol (E2) increases AMPK activity in c2c12 myotubes, as well as in human ductal breast epithelial tumor cells (T47D). Further, AMPK activity is potentiated by chemical as well as siRNA inhibition of the individual Estrogen Receptors (ERα or ERβ), suggesting an antagonistic effect of the two Estrogen Receptors (ER) on AMPK activation. Next, we hypothesized that E2 regulates AMPK through a direct interaction of ER and AMPK. Using co‐immunoprecipitation in neonatal rat cardiomyocytes and female mice hearts, we show a direct interaction of ERβ with AMPK and MO25, a component of the upstream AMPK activation complex. We conclude that E2 can activate the AMPK through a direct interaction of ERβ with members of the AMPK kinase complex.Grant Funding Source: Supported by R01 HL098256A
Quantitative and qualitative examination of 2D versus 3D technologies in teaching anatomy (211.7)
Authors: Peterson Diana 
Published: June 2021

The primary purpose of the study was to identify whether three‐dimensional technologies significantly improved the knowledge and comprehension levels of students within a gross anatomy curriculum compared to the traditional two‐dimensional figures. We hypothesized that the use of 3D technologies would dramatically enhance the comprehension and retention of students.We tested our hypotheses in a graduate and undergraduate level gross anatomy curriculum. Students were presented 2D images and 3D study materials (atlases, videos, and animations). All material was presented to the students over blackboard; and individual student usage of all material was tracked throughout the semester (# views, time of viewing, and dates of usage).Subjective measures of student opinion were taken using student surveys. To provide a quantitative measure of student interest, the number of views for each type of study material was calculated. This calculation was then compared with the subjective student evaluations.To provide a quantitative measure for learning comprehension, half of the test questions were presented from the 2D and the other half from the 3D study materials. Test scores for questions covering 2D versus 3D material were then compared within each student and between students to determine whether the student’s opinion about their learning improvements was substantiated with their test results.Subjective results indicate that students were much more interested and engaged with the 3D study materials. Although they prefer 3D materials verbally, students tended to rely more heavily on 2D materials when studying prior to tests and 3D materials when not cramming. Preliminary test results indicate that the student scores on 3D material were better than that of 2D material. As expected, student usage of all study materials increased an individual’s overall scores. Given this bias, the percentage of time utilizing 2D versus 3D study materials, was also positively correlated with improved score.Grant Funding Source: Supported by Iowa State University Miller Fellowship
Big shifts in anatomy education (215.1)
Authors: Wade Patricia Ann 
Published: June 2021

Anatomy instruction is evolving. For some courses, this means fewer lectures, more pre‐class assignments, more in‐class small group activities, and more online and computer‐delivered learning activities. What is the rationale behind these changes in anatomy instruction? Which changes in instruction result in increased mastery of the course material? How does an instructor select the best learning tools and teaching methods for their students? By participating in this session, you will be able to: * Describe the key features of active learning, supporting theories, and evidence.* Discuss various types of active learning, including the flipped classroom format and independent study methods for anatomy courses.* List several types of instructional strategies and learning tools for courses in anatomy and other basic science courses.* Select instructional methods and learning tools that will enhance motivation and mastery of anatomy for students in your classroom.
Making three dimensional human colored skin by using Muse cells, a novel type of non‐tumorigenic pluripotent stem cells (216.3)
Authors: Dezawa Mari 
Published: June 2021

We found mesenchymal tissues such as the dermis, bone marrow and adipose tissue and commercially available cultured mesenchymal cells such as fibroblasts hold Multilineage differentiating Stress Enduring (Muse) cells, non‐tumorigenic pluripotent stem cells. We show that human dermal fibroblast‐derived Muse cells are readily reprogrammable into melanin pigment‐producing functional melanocytes by use of certain combinations of factors. Muse cells expressed melanocyte markers including tyrosinase and MiTF and to show positivity for the L‐DOPA reaction, an indicator of melanin production. We then tried to artificially construct colored human skin tissue incorporated with Muse‐derived melanocytes in 3D culture. The dermis was constructed by human fibroblasts and extracellular matrix, and the epidermis by human keratinocytes and Muse‐derived melanocytes. Muse‐derived melanocytes localized themselves in the basal layer of the epidermis and produced melanin in the same manner as authentic melanocytes. This 3D constructed human artificial skin also maintained their melanin production even after the tissue was transplanted to immunodeficient mice back skin. This technique may contribute to autologous transplantation for melanocyte dysfunctions such as vitiligo as well as substituting animal experiments for cosmetic development and drug test.Grant Funding Source: NEDO, Japan
MOOCing STEM courses: for what purpose and which audiences? (221.1)
Authors: Green Kenneth 
Published: June 2021

The continuing campus, public, and even state legislature conversations about the big (massive!) enrollments in the first waves of MOOCs, coupled with a course inventory that includes lots of higher end (upper‐division and graduate‐level) STEM courses, has served as a catalyst for great aspirations and broad discussion about using MOOCs to transform the delivery and the learner experience in STEM courses. Yet a careful examination of several key issues, including content development, instructional infrastructure, and assessment/certification, suggests that any effort “to MOOC” core STEM courses will require the significant investment of time, money, and other resources on the part of professors, instructional support personnel, and academic programs. Moreover, credit remains the coin of the realm in academe: awarding credit and certifying competency pose real challenges for those who wish to leverage MOOCs to advance and enhance STEM education.BIO: Kenneth C. Green is the founding director of The Campus Computing Project, the largest continuing study of eLearnng and information technology in American higher education. From 1983‐89 Green was the associate director of UCLA's Higher Education Research Institute where he was involved in research on STEM pipeline issues.
Impact of a human missense UCP3 polymorphism on the plasma metabolomic profile: support for a mitochondrial fuel‐partitioning role for UCP3 (248.4)
Authors: Piccolo Brian , Grapov Dmitry , Garvey W. Timothy , Harper Mary‐Ellen , Fiehn Oliver , Adams Sean , Newman John 
Published: June 2021

Skeletal muscle uncoupling protein 3 (UCP3) is thought to facilitate fatty acid oxidation (FAO) and protect against excess mitochondrial (MITO) reactive oxygen species (ROS); however, this has yet to be conclusively proven in human studies. We hypothesized that a comprehensive plasma metabolomic characterization of a human UCP3 polymorphism would identify metabolites associated with decreased skeletal muscle FAO and oxidative stress. We measured 490 metabolites using three independent metabolomics platforms in obese African‐American women with or without type 2 diabetes (T2D) containing a missense G304A (G/A) UCP3 polymorphism. Partial least squares‐discriminant analysis (PLS‐DA) revealed altered amino acid profiles and metabolites consistent with enhanced glycolytic oxidation in the context of reduced UCP3 function. UCP3 G/A genotype also revealed decreases in plasma amino acids involved in glutathione metabolism and markers of glutathione synthesis. Stearoylethanolamide (SEA), a putative modulator of MITO oxidative phosphorylation and biogenesis was also significantly elevated in T2D UCP3 G/A individuals. Our results support the idea that UCP3 is involved in regulating muscle MITO fuel selection by promoting fatty acid combustion, perhaps via mechanisms involving ROS signaling.Grant Funding Source: Supported by: NIH‐NIDDK R01DK078328‐01, UAB‐CCTS UL1 RR025777, WCMC NIH 1 U24 DK097154, USDA‐ARS
Metabolomic profiles of childhood obesity and cardiometabolic risk (248.6)
Authors: Perng Wei , Gillman Matthew , Watkins Steve , Patti Mary‐Elizabeth , Fleisch Abby , Oken Emily 
Published: June 2021

Objective To identify metabolite patterns associated with childhood obesity, and to examine their relations with cardiometabolic risk biomarkers.Methods We quantified 350 metabolites in serum of 262 children 7‐10 y with an untargeted mass spectrophotometry approach. Using principal component analysis, we characterized 18 metabolite patterns. Next, we compared factor scores for each pattern between obese (BMI 蠅 95 %tile; n = 84) and lean children (BMI < 85 %tile; n = 150) to identify patterns related to obesity. Using multivariable linear regression we examined relations of the metabolite factor scores with ln transformed HOMA‐IR, leptin, adiponectin, triglycerides, CRP, and IL‐6.Results Approximately half (50.6%) of the sample were boys; 58.9% were white. Compared to lean children, obese children had higher factor scores for a branched chain amino acid (BCAA) and an androstene steroid (AS) pattern. After adjustment for age, sex, and race, every 1 unit increment in the BCAA score corresponded to 7% (1%, 14%) higher HOMA‐IR, 15% (6%, 25%) higher leptin, and 31% (14%, 49%) higher CRP. Each unit of the AS score was associated with 4% (1%, 7%) higher triglyceride levels, 7% (2%, 11%) lower adiponectin, and 12% (3%, 20%) higher IL‐6.Conclusions: BCAA and steroid metabolite profiles associated with obesity are also related to established biomarkers of cardiometabolic risk during mid‐childhood.Grant Funding Source: National Institutes of Health
Effect of delivering a comprehensive package of services on nutritional status of people living with HIV and AIDS referred for HIV treatment in Rwanda (251.5)
Authors: Lopez Melanie , Muhinda Bosco , Dhlamini Russell 
Published: June 2021

Objective: To improve nutritional status for PLWHA referred to HIV treatment by providing an integrated package of clinical nutrition, food security (FS), and economic strengthening services.Methods: Integrated nutrition services and monitoring of body mass index (BMI); agricultural services such as Farmers Field Schools (FFS) and use of Bio‐Intensive Agricultural Techniques (BIAT); and access to savings and lending schemes (SILC) were provided for 7000 participants referred for HIV treatment across six districts in Rwanda. Pre‐ and post‐test surveys were conducted to assess change in BMI.Results: Severe malnutrition levels (BMI <16kg/m2) of beneficiaries decreased from 4.6% in 2009 to 0.9% in 2011 and 0.1% in 2013. 92% of beneficiaries adopted at least three BIAT techniques and they reported 3 to 5 times increased production of vegetables. 80% of SILC groups increased their monthly subscription from 500 RWF (Rwandan Francs) to between 1000 to 1500 RWF.Conclusion: Integrating nutrition, agriculture and economic empowerment interventions for PLWHA appears to have positive effects on BMI, as well as FS and socioeconomic status, for PLWHA.Grant Funding Source: Catholic Relief Services through the United States President’s Emergency Plan for AIDS Relief (PEPFA
Intermittent bolus feeding enhances vital organs growth compared with continuous feeding in neonates (258.7)
Authors: El‐Kadi Samer , Boutry Claire , Suryawan Agus , Gazzaneo Maria , Orellana Renan , Srivastava Neeraj , Nguyen Hanh , Kimball Scot , Fiorotto Marta , Davis Teresa 
Published: June 2021

Orogastric tube feeding provides enteral nutrition to critically ill neonates unable to ingest normally, and can be administered by intermittent bolus (INT) or continuous (CON) infusion. Recently, we showed that INT compared to CON feeding enhances lean tissue accretion by increasing muscle protein synthesis in neonates. The aim of this study was to determine if these feeding modalities affect vital organ growth. Neonatal pigs (n=6, 6‐d‐old) were fed the same diet in equivalent amounts continuously or intermittently (meal every 4h) for 21d. Arterial branched‐chain amino acid and insulin concentrations measured on the last day of feeding were greater for INT after the meal than for CON pigs (P<0.05). Protein synthesis increased by 14% in jejunum, 48% in ileum, and 22% in liver of INT compared to CON pigs (P<0.05), while for the kidneys the increase was only modest. Jejunum, ileum, liver and kidneys were 41, 36, 73 and 55% heavier for pigs in the INT as compared to the CON group (P<0.05). Phosphorylation of ribosomal protein S6 kinase were higher in ileum and liver in INT compared to CON fed pigs indicating increased translation initiation (P<0.05). The proportion of rpS8 mRNA associated with polysomes in liver was greater in the INT compared to CON fed group (P<0.05). These results suggest that intermittent feeding enhances vital organ growth by up‐regulating protein synthesis.Grant Funding Source: Supported by NIH AR444474 and USDA/ARS 6250‐51000‐055