bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the upper respiratory tract of Neanderthals and other later Pleistocene human fossils: analysis of form and function (17.6)
Authors: Márquez Samuel , Pagano Anthony , Delson Eric , Laitman Jeffrey
Published: June 2021

Neanderthals are one of the most intensely studied groups of extinct humans, as aspects of their phylogeny and functional morphology remain controversial. They have long been described as cold adapted but recent analyses of their nasal anatomy suggest that traits formerly considered adaptations may be the result of genetic drift. Here we describe our previous and current studies on the nasal complex (NC; nose, nasal cavity, nasopharynx, connecting pathways) of Neanderthals and other later Pleistocene fossils from Europe and Africa. A geographically diverse sample of modern human crania was used to establish an anatomical baseline for populations inhabiting cold and tropical climates. Nasal complex morphology was analyzed via traditional and geometric morphometrics and CT imaging. Results indicate that Neanderthals possessed NC's that fall outside the range of modern human variation in several traits, including paranasal sinus morphology. In particular, they exhibited greater relative piriform aperture area (the product of width and height) and a relatively longer cartilaginous Eustachian tube as measured from Procrustes‐corrected sets of three‐dimensional coordinate data. The NC components of the upper respiratory tract remain a critical but poorly understood area that may yet offer novel insight into one of the greatest continuing controversies in paleoanthropology.

Grant Funding Source: Supported by NSF and IGERT
Duodenal expression of heme and non‐heme iron transporters and tissue partitioning of dietary heme and non‐heme iron in a rat mode of iron overload (246.8)
Authors: Cao Chang , Thomas Carrie , Insogna Karl , O'Brien Kimberly
Published: June 2021

Dietary heme is an important Fe source yet the regulation of heme absorption and tissue partitioning of absorbed heme remain undefined. In a rat model of Fe overload, we aimed to 1) examine duodenal heme and non‐heme Fe transporters in relation to hepcidin, and 2) to compare utilization of absorbed heme and non‐heme Fe by erythroid (RBCs) and Fe storage tissues (liver and spleen). Twelve male Sprague Dawley rats were randomized to receive injections of PBS (control) or Fe dextran providing a total of 16 mg (Moderate Fe) or 48 mg Fe (High Fe) over 2 weeks. After Fe loading, rats were gavaged with 57Fe‐FeSO4 and 58Fe‐porcine RBC. Duodenal Fe transporter expression and tissue isotopic enrichment were assessed 10‐days post‐dosing. Fe injection in the High Fe group suppressed duodenal transcript expression of divalent metal transporter 1 (Dmt1) and duodenal cytochrome b (Dcytb) by 70% but did not impact heme carrier protein 1 (Hcp1) or Ferroportin. Liver hepcidin expression correlated with Dmt1, Dcytb and Ferroportin but not with Hcp1. Tissue isotopic analysis found greater non‐heme than heme Fe incorporation into RBC (80.5% vs. 71.3%, p = 0.02) while this relationship was reversed in the spleen (2.7% vs. 7.5%, p = 0.01). Fe status and hepcidin had no impact on duodenal Hcp1 expression. Differential tissue utilization of absorbed heme vs. non‐heme Fe suggests that heme Fe is exported in an alternate form from non‐heme Fe.

Grant Funding Source: Supported by USDA 2008‐0857
Clinical and metabolomic predictors of weight loss in overweight and obese adults in an energy‐restricted controlled feeding trial (248.5)
Authors: Piccolo Brian , Newman John , Gertz Erik , Woodhouse Leslie , Souza Elaine , Gustafson Mary , Sheets Caitlin , Fiehn Oliver , Keim Nancy , Adams Sean , Van Loan Marta
Published: June 2021

Weight loss (WL) induced by energy restriction is highly variable even in controlled clinical trials. An integrative analysis of the plasma metabolome coupled to traditional clinical variables may reveal a WL “responder” phenotype. Therfore, we predicted WL in overweight and obese individuals on an energy‐restricted diet in a controlled feeding trial using the plasma metabolome in addition to clinical indices, body composition parameters, plasma endocrine and inflammatory markers, dietary parameters, and physical activity (PA) measurements. A total of 940 pre‐intervention (PrI) and post‐intervention (PoI) variables were assessed. Partial least squares regression accurately predicted weight loss along latent variable 1 (root mean error of prediction (RMSEP) = 1.81 kgs; Q2 = 0.43) and revealed that PrI light and moderate PA were associated with high weight loss, whereas PoI sedentary PA and 2‐ketoisocaproic acid were associated with low weight loss. Network correlation analysis revealed a direct connection between lower PrI respiratory quotient, higher PoI 3‐hydroxybutanoic acid and higher PoI citric acid (P < 0.00001) in high weight losers. Our results suggest that habitual light‐to‐moderate PA are accompanied by distinct blood amino acid and lipid metabolic signatures and correlated with WL in overweight and obese individuals under controlled conditions.

Grant Funding Source: Supported by: Nat. Dairy Council; CA Dairy Res. Council; USDA; NCRR (UL1 RR024146); NIH (U24 DK097154)
Optimization of calcium and vitamin D status during initial military training: a randomized, double‐blind, placebo‐controlled trial (250.4)
Authors: McClung James , Gaffney‐Stomberg Erin , Lutz Laura , Rood Jennifer , Cable Sonya , Pasiakos Stefan , Young Andrew
Published: June 2021

Poor vitamin D status is linked to musculoskeletal injuries, such as stress fracture, during military training. The objective of this trial was to determine the effect of daily calcium (Ca) and vitamin D supplementation (2000 mg and 800 IU/day, respectively) on biochemical indicators of nutritional status and bone health, including ionized Ca (iCa), serum vitamin D (25[OH]D), and parathyroid hormone (PTH) during initial military training (IMT). Biomarkers were assessed in volunteers (n = 164, males = 104, females = 60, age [mean ± SD] = 21 ± 4 yrs) at the start of IMT (PRE), and at the end of the 9‐wk course (POST). Supplemental Ca and vitamin D were provided in a fortified snack food, which was consumed 2x/day throughout IMT; overall compliance was 84%. As compared to placebo, Ca and vitamin D supplementation resulted in increased circulating iCa POST‐IMT (group X time interaction, P < 0.05), but not serum 25(OH)D. Increased PTH levels observed in the placebo group at the end of IMT (PRE vs. POST, P < 0.05; 28.5 ± 13.2 vs. 31.3 ± 16.3 pg/ml) were attenuated in the supplemented group (group X time interaction, P < 0.05; 26.9 ± 12.7 vs. 25.3 ± 13.7). Although serum 25(OH)D was not affected, these data indicate that supplementation with Ca and vitamin D during IMT resulted in positive changes in Ca status by preventing the mobilization of Ca from bone through stabilization of PTH. Research supported by USAMRMC.
A church‐based, diet and supervised physical activity intervention for rural, southern African American adults improves diet quality, physical activity, and blood lipids (251.6)
Authors: Tussing‐Humphreys Lisa , Thomson Jessica
Published: June 2021

Epidemic levels of obesity, diabetes, hypertension, and heart disease are rampant in the largely rural Lower Mississippi Delta (LMD) region. We assessed the effectiveness of a six‐month, church‐based, diet and supervised physical activity (PA) intervention for improving diet quality (measured by the Healthy Eating Index‐2005) and increasing PA of LMD African American adults. Eight churches were assigned to intervention (n=5) or control (n=3). The intervention involved 9 one hour group didactic sessions and weekly supervised PA. Assessments included dietary, PA, anthropometric, and clinical measures. Statistical tests for group comparisons included chi square and McNemar’s tests for categorical variables, and mixed model regression for continuous variables. Retention was 79% (96/122) for control and 76% (217/287) for intervention churches. Several diet quality components, including fruit, vegetables, and total quality improved significantly in the intervention group. Similarly, increases in PA were apparent in the intervention group, while PA decreased in the control group. Significant decreases in blood lipids and trending (0.05 < p 蠄 0.10) reductions in weight and BMI were observed for the intervention group. Results from this study indicate that a church‐based, diet and supervised PA intervention improves diet quality and increases PA of LMD African American adults.

Grant Funding Source: Funding was provided by US DHHS HRSA Grant # 6 U1FRH07411 and the USDA Agricultural Research Service
Link of maternal restriction versus reward to child obesity and BMI differs with level of maternal education (252.6)
Authors: Hubbs‐Tait Laura , Shriver Lenka , Okwonga Ajok , Kimble Ashley , Page Melanie , Topham Glade , Harrist Amanda
Published: June 2021

Study objective was to evaluate separate relations of maternal Child Feeding Questionnaire (CFQ) restriction and reward to child obesity for maternal education subgroups to clarify the debate on restriction as cause vs. consequence of obesity. Participants were 245 mothers and children (135 boys) followed from 1st to 3rd grade. Maternal education subgroups: 25% high school only; 38% vo‐tech graduates/some college; 37% college graduates. CFQ was measured when children were 1st graders; child anthropometrics, annually. Restriction scores were: CFQ Restrict6 (6 items, α=.70) and CFQ Reward (2 items, α=.80). For children of college graduates, Restrict6 was linked to BMI and odds of obesity in 1st grade (OR=3.40, p = .046). For children of vo‐tech/some‐college mothers, CFQ Reward predicted child BMI and odds of obesity in 1st (OR=2.08, p=.01), 2nd (OR=1.17, p=.02), and 3rd (OR=1.53, p=.07) grade. For children of high‐school‐only mothers, Restrict6 and Reward were unrelated to BMI and obesity. Thus, only for children of college‐educated mothers could CFQ Restrict6 be a response to child obesity in 1st grade. For children of vo‐tech/some college mothers, Reward might cause obesity or maintain it over time. Given the different relations of maternal restriction and reward to child obesity by education level, new obesity prevention efforts are needed that target unique behaviors of subgroups of parents.

Grant Funding Source: Supported by USDA 2004‐05545
Quantification and bioaccessibility of California pistachio bioactives (259.1)
Authors: Liu Yuntao , Blumberg Jeffrey , Chen C‐Y.
Published: June 2021

Pistachios (Pistacia vera L.) contain an array of bioactives including carotenoids, chlorophylls, phenolics, and tocols. The content of these constituents has not been methodically quantified. Our objective was to optimize extraction protocols for lipophilic nutrients and then quantify the content of 20 bioactives (2 phenolic acids, 9 flavonoids, 4 carotenoids, 2 chlorophylls, and 3 tocols) in the skin, nutmeat, and whole nut of California pistachios. The dominant bioactives in whole pistachios are lutein (42.35 µg/g fresh weight), chlorophyll A (142.24), γ‐tocopherol (182.20), flavan‐3‐ols (catechins) (199.18), luteolin (217.89), myricetin (135.18), and cyanidin‐3‐galactose (38.34) in each nutrient class. Most phenolics are present in the skin except luteolin and myricetin, while the lipophilic nutrients are dominantly present in the nutmeat. Digestion with a gastrointestinal mimic employed to approximate the bioaccessibility of pistachio constituents showed <10% of most hydrophilic compounds are released from pistachio matrices, as well as <7% of lutein and γ‐tocopherol. In conclusion, 9 lipophilic and 11 hydrophilic bioactives in California pistachios have been systematically quantified. (Supported by American Pistachio Growers and USDA)

Grant Funding Source: Supported by American Pistachio Growers and USDA
Inhibitory effects of epoxy metabolites of docosahexaenoic acid on human colon cancer stem cells (261.3)
Authors: Xu Fei , Lee Sing , Hammock Bruce , Zhang Guodong , Xiao Hang
Published: June 2021

Epidemiological and preclinical evidence supports that omega‐3 dietary fatty acids such as DHA reduce the risks of cancers, but the underlying mechanisms are poorly understood. Epoxydocosapentaenoic acids (EDPs) are the cytochrome P450 epoxygenases (CYP450) metabolites of DHA, and have been reported to mediate some of the health‐promoting effects of DHA. Increasing evidence suggests that cancer stem cells (CSCs) may be responsible for occurrence of malignant tumors. Herein we investigated the inhibitory effect of EDPs on human colon CSCs. CSC‐ associated tumor spheres were obtained from human cancer stem cells. The inhibitory effect of 19, 20‐EDP and a mixture of six different EDPs (i.e. 7‐, 8‐, 10, 11‐, 13, 14‐, 16, 17‐ and 19, 20‐EDP) were determined on both HT29 and HCT116 colon cancer cells. The results showed that both 19, 20‐EDP and EDPs mix showed a dose‐dependent inhibition on human colon CSCs. For example, treatment with 19, 20‐EDP at 1µM for 10 days caused 55% inhibition on tumor spheres derived from HT29 cells, while EDPs mix at same total concentration caused 71% inhibition. Most interestingly, 19, 20‐EDP and EDPs mix at a very low concentration of 0.1 µM still resulted in significant inhibition (33% and 55%, respectively) on tumor spheres derived from HT29 cell line. Overall, our study for the first time demonstrated the inhibitory effects of EDPs on human colon CSCs.

Grant Funding Source: Supported by funding from NIH, AICR and USDA
Vitamin D/Ca2+‐dependent calpain and caspases: novel molecular targets for obesity‐related breast cancer drug discovery (261.5)
Authors: Sergeev Igor
Published: June 2021

Removal of breast cancer cells (BCC) via apoptosis results in a decrease in tumor size. Induction of apoptosis in adipocytes decreases adiposity due to long‐term reduction in adipose tissue mass. The hormone 1,25(OH)2‐vitamin D3 (1,25D) triggers apoptosis in both BCC and mature adipocytes via apoptotic Ca2+ signal ‒ a sustained increase in intracellular Ca2+. This signal acts as an initiator of apoptosis that directly recruits Ca2+‐dependent apoptotic effectors, calpain and caspase‐12, in BCC and adipocytes. Normal mammary epithelial cells are resistant to Ca2+‐mediated apoptosis because Ca2+ regulatory mechanisms in these cells do not support the apoptosis‐inducing Ca2+ signal. Remarkably, high vitamin D and Ca intakes activate Ca2+‐mediated apoptotic pathway in adipose tissue and decrease body and fat weight gain in obese mice. Induction of apoptosis with 1,25D in adipocytes, particularly in the tumor‐surrounding adipose tissue involved in tumor progression, contributes to anticancer effects of the hormone. The 1,25D ‒ Ca2+ link between breast cancer and obesity supports rationale to include the vitamin D/Ca2+‐dependent apoptotic proteases as molecular targets for discovery of new therapeutic and preventive agents for breast cancer and obesity as well as to consider increasing vitamin D and Ca intakes as a promising approach to protecting against breast cancer and decreasing adiposity. Supported by USDA 2009‐35200‐05008 and SD00H325.

Grant Funding Source: Supported by USDA
Association between 100% fruit juice consumption and nutrient intake, diet quality, and weight in children (2‐18 yrs.): National Health and Nutrition Examination Survey (NHANES) 2007‐2010 (262.8)
Authors: Nicklas Theresa , Rodriguez Gabriela , O'Neil Carol , Fulgoni Victor
Published: June 2021

The association between 100% FJ consumption with nutrient intake, diet quality, and weight was examined in children (n=6,090) using NHANES (2007‐2010) data. Consumers (n=2,337; 34%) were defined by four categories of 100% FJ consumption using a 24‐hour diet recall. Trend analysis (covariate adjusted) was conducted using appropriate sample weights. Logistic regression was used to determine odds ratios. Diet quality was calculated using the Healthy Eating Index‐2010 (HEI). Mean 100% FJ consumption was 3.6 oz/d, which contributed a mean of 47 kcal (2.6% of total energy intake). Compared with non‐consumers, children consuming 100% FJ had significantly increased (p<0.01) intakes of energy, carbohydrates, potassium, magnesium, and vitamins C and B6 and significantly (p<0.01) lower intakes of total fat, SFA, solid fat, added sugar, and sodium. Children consuming 100% FJ consumed significantly (p<0.01) more servings of whole fruit than non‐consumers; no differences were found in milk consumption. The total HEI score significantly increased (p<0.0001) with increased 100% FJ consumption (43.8 for 0 oz. to 52.3 for (>12 oz). There was no difference in the likelihood of being overweight/obese between 100% FJ consumers and non‐consumers. 100% FJ consumption was not excessive and was associated with better nutrient intakes and was not associated with the likelihood of being overweight/obese in children.

Grant Funding Source: Supported by: Juice Products Association & USDA
The Shaping Healthy Choices Program results in improved nutrition and health‐related outcomes (273.6)
Authors: Scherr Rachel , Linnell Jessica , Smith Martin , Nicholson Yvonne , Spezzano Theresa , Bergman Jacqueline , Brian Kelley , Briggs Marilyn , Feenstra Gail , Hillhouse Carol , Keen Carl , Nguyen Lori , Ohmart Jeri , Ontai Lenna , Steinberg Francene , Sutter Carolyn , Young Heather , Zidenberg‐Cherr Sheri
Published: June 2021

The Shaping Healthy Choices Program (SHCP) is a school‐based intervention that integrates 5 components: nutrition education; family and community partnerships; regional agriculture; foods available on school site; and school wellness policies. This study tests the hypothesis that schools using the SHCP during one school year will improve health‐related outcomes. Schools meeting inclusion criteria in Northern (NC) and Central Valley California (CV) were randomly assigned to control (C) or intervention (I) groups. Pre‐ and post‐assessments in 4th graders included: ability to name vegetables, using the Vegetable Preference Survey; dietary intake, using the Block Food Frequency Questionnaire; and anthropometric data such as BMI. Students at the I schools scored higher than students at the C schools on the ability to correctly name vegetables. A 40% increase (P < 0.01) in vegetable intake servings per day (s/d) was observed in students who consumed 1 or less s/d at baseline at the NCI school; no differences were observed at other schools. Decreases in BMI (‐2.55, P< 0.001) and BMI percentile (‐8.87, P < 0.001) were observed at the NCI school; no differences were observed in other schools. Change in BMI percentile was negatively correlated with vegetable intake at the NCI school (r = ‐0.25; P < 0.02). The SHCP is a promising model for school‐based programs aimed at improving nutrition and health outcomes in students.

Grant Funding Source: Supported by UCANR #11‐1018 & USDA 2011‐38420‐20082
A model dilemma: how assumptions about locomotion and birth have shaped the obstetrical dilemma (335.1)
Authors: Warrener Anna
Published: June 2021

The obstetrical dilemma posits that the human female pelvis is under antagonistic selection pressures: narrow enough for efficient locomotion, but large enough to pass a large‐brained infant through the birth canal. This adaptive trade‐off is thought to explain the apparent difficulty of human childbirth, the helplessness of human neonates, and sex differences in human locomotor performance. However, core assumptions of the obstetrical dilemma model have gone untested. One assumption, that wider pelves in women increase locomotor cost, is based on a static biomechanical model of hip abductor function. Wider biacetabular width is thought to increase the external torque about the hip by moving the body center of mass farther from the hip joint, thereby increasing hip abductor muscle force and energetic cost to stabilize the pelvis. However, skeletal dimensions are actually poor proxies for the mechanical determinants of hip abductor function measured during locomotion and do not correlate significantly with locomotor cost. While this first assumption of the obstetrical dilemma can be empirically rejected, it is harder to directly assess the bases for and evolutionary history of cephalopelvic disproportion (CPD) that uniquely imperils human birth. A novel hypothesis to be tested suggests that recent environmental conditions have made CPD more common today than through most of human evolutionary history.

Grant Funding Source: National Science Foundation BCS#0850841, The Leakey Foundation, The Wenner‐Gren Foundation
Neural crest αN‐catenin function in cranial ganglia assembly (344.1)
Authors: Taneyhill Lisa
Published: June 2021

Neural crest cells are crucial for proper vertebrate development, building the craniofacial skeleton and, together with epidermal placode cells, the cranial ganglia of the peripheral nervous system. Defective ganglia function can lead to conditions such as neuralgia and peripheral neuropathies and contribute to other diseases. Migratory neural crest cells are generated from immotile precursors possessing adherens junctions composed of cadherins and αN‐catenin, a protein that also controls formation of central nervous system structures. Although αN‐catenin down‐regulation is critical for initial neural crest cell emigration from the neural tube, a later role for αN‐catenin in the peripheral nervous system is not known. To this end, we evaluated αN‐catenin spatio‐temporal distribution and perturbed αN‐catenin function to elucidate effects on cranial trigeminal ganglia formation in the chick. We find that migratory neural crest cells forming the trigeminal ganglia re‐express αN‐catenin and, as in the trunk, express Cadherin‐7. αN‐catenin perturbation alters trigeminal ganglia assembly through changes in neural crest and placode cell contribution to the ganglia as well as Cadherin‐7 distribution and levels. Importantly, αN‐catenin function is likely conserved in other cranial ganglia. Together, our results highlight a novel role for neural crest cell αN‐catenin in cranial gangliogenesis.

Grant Funding Source: Supported by NSF IOS‐0948525
Assessing student skills in laboratory and research experiences (348.4)
Authors: Caldwell Benjamin
Published: June 2021

Undergraduate students completing biochemistry and molecular biology programs need not only a firm grasp on the essential concepts of the field, but they also need the skills to use and communicate that knowledge. Through a series of workshops supported by an RCN‐UBE grant, ASBMB has been working to build a network of BMB faculty to identify the essential skills students should have upon completing their undergraduate training. Over the course of two years workshop participants identified key skills BMB students should possess in order to move into the workforce or go on to graduate or professional schools. Having the ability to work reliably in the laboratory is an obvious target. Students should know how to develop a hypothesis, design experiments using appropriate methods and controls and be able to analyze and interpret data. They should be able to search for and capably read primary literature, and as well as knowing how to use data bases and internet based resources. In addition to these skills, students should have a firm understanding of to work safely in a laboratory. They should also know how science is communicated to a variety of audiences (peers and lay people). Gauging the ability of students to perform tasks and skills and the state of effective skills based assessment tools for measuring student capabilities in the laboratory and beyond will be discussed. Supported by NSF Grant 0957205.
Food sources of flavonoids for adults in the United States: What We Eat in America, NHANES 2007‐2008 (369.5)
Authors: Sebastian Rhonda , Goldman Joseph , Wilkinson Enns Cecilia , Martin Carrie , Steinfeldt Lois , Dwyer Johanna , Moshfegh Alanna , Milner John
Published: June 2021

Flavonoids are compounds from plants that may play important roles in preventing chronic diseases including heart disease and cancer. This study’s objective was to identify top food contributors of 6 classes of flavonoids (including only the 29 most predominant dietary flavonoids) to the diets of American adults. One day of dietary data from 5,420 adults age 蠅20 years in What We Eat in America (WWEIA), NHANES 2007‐2008 was analyzed. Based on a preliminary version of USDA’s Expanded Flavonoid Database for the Assessment of Dietary Intakes, flavonoid values were calculated for every food in USDA’s Food and Nutrient Database for Dietary Studies 4.1, the database used in coding foods reported in WWEIA 2007‐2008. Similar foods were grouped using the WWEIA Food Categories before determining percentage contributions to flavonoid intake. Overall, tea accounted for 81% of total flavonoid intake. Tea was also the food category providing the largest percentage of flavan‐3‐ols (94% of total) and flavonols (40% of total). Other top contributors to intake of flavonoid classes were soy‐based protein powders (isoflavones); berries and wine (anthocyanidins); citrus fruits and juices (flavanones); and mixed dishes and vegetables (flavones). Findings derived using new public‐use databases can inform efforts to monitor flavonoid intakes and educate the public about connections between foods and health.

Grant Funding Source: Supported by ARS, USDA, with additional funding provided by the Office of Dietary Supplements
A cell death assay for assessing the mitochondrial targeting of proteins (373.3)
Authors: Teixeira Daniel , Cordonier Elizabeth , Wijeratne Subhashinee , Huebbe Patricia , Jamin Augusta , Jarecke Sarah , Wiebe Matthew , Zampleni Janos
Published: June 2021

Some of the 800 mitochondrial diseases are linked with aberrant protein localization. We devised a high‐throughput cell survival assay for assessing mitochondrial localization of proteins. Cells are transfected with plasmids coding for fusion constructs of mitochondrial proteins and the peptide KLAKLAKKLAKLAK (KLAK), which disrupts the mitochondrial membrane potential and causes cell death; cell survival of KLAK fusion proteins and empty KLAK plasmids (control) is assessed using the MTT assay (ΔMTT). KLAK fusion constructs of proteins that localize in mitochondrial membrane (acetyl‐CoA carboxylase 2, ACC2, carnitine palmitoyltransferase 1, and uncoupling protein 1), or are of uncertain mitochondrial localization (holocarboxylase synthetase), produced ΔMTT values between 0.211 and 0.411. The assay has a wide dynamic range (Z‐Prime = 0.58) and a low coefficient of variation (4.8%). The assay is also useful to investigate effects of bioactive compounds on the mitochondrial localization of proteins, evidenced by the observation that chlorogenic acid and gallic acid increased cell survival by 131% and 78%, respectively, in HEK293 transfected with ACC2‐KLAK, presumably due to a loss of mitochondrial ACC2. We conclude that our assay identifies both mitochondrial proteins and compounds that alter mitochondrial localization.

Grant Funding Source: Supported by ARD Hatch, NIFA, and NIH.
The assets of ASSET: improving surgical performance confidence through an anatomy and skills review course for surgeons (536.11)
Authors: Garofalo Evan , Shackelford Stacy , Holmes Megan , Mackenzie Colin , Bowyer Mark
Published: June 2021

Rapid control of major hemorrhage is a primary goal in trauma surgery. However, many surgeons have little practical experience with the required vascular exposures. To address this, the American College of Surgeons developed the Advanced Surgical Skills for Exposure in Trauma (ASSET) course to review anatomy, skills and techniques for major vascular exposures. Since 2008, a broad range of participants have attended, including surgeons of many specialties, deploying military surgeons and surgery residents.

We compared self‐reported confidence of participants (n=562) in surgical tasks (n=47) at baseline and directly after ASSET training to examine the effect of the course stratified by surgical experience level (resident/fellow; <8 years post‐residency; 8+ years post‐residency), specialty (trauma/vascular; general surgery; other specialties), and body region.

Results of Freeman‐Halton 3x2 tests indicated significant gains in confidence scores for all specialties (p<0.02), particularly for general surgeons (p<0.01) and exposures in the chest (p<0.001), after ASSET. There was no difference in confidence gained by surgical experience. This study demonstrates the value of continuing education in applied anatomy for clinical practice. Given the frequency of vascular trauma in current military conflicts, the impact of ASSET is particularly relevant for preparing deploying surgeons for the theatre.

Grant Funding Source: Supported by: US Army W81XWH‐13‐2‐0028
Site‐specific variation in cortical porosity and histomorphometry as a reflection of growth and mechanical adaptation in the human tibia (541.12)
Authors: Goldman Haviva , Hampson Naomi , Guth J , Kent Lindsey , Lin David , Rajapakse Chamith , Jepsen Karl
Published: June 2021

Previous research has shown that individuals with more slender (narrow relative to length) tibiae may suppress remodeling as a means of increasing tissue stiffness. To test this hypothesis, we quantified cortical porosity (using µCT) and histomorphometry (using light microscopy) in human cadaveric tibia samples (N=10; obtained from 38% and 66% distance proximal to distal endplate) and examined correlations with robustness (total cross‐sectional area/length) and elastic modulus (determined by finite element analysis). Data were analyzed for whole cross‐sections and by anatomically determined regions of interest (ROIs) to determine site‐specific variability.

Porosity and histomorphometric variables correlated significantly with robustness (at 66%) and elastic properties, suggesting that remodeling was modulated relative to robustness and affected bone properties at a local level. In addition, anatomical location was a significant (p < 0.001) predictor of variability in all histological measures. This variation could be explained by expected anterior‐posterior [AP] bending loading, as well as by variation in tissue age due to medial drift patterns during growth. Both loading and growth history need to be considered, in addition to global regulators of remodeling such as robustness, when interpreting intra and inter‐individual variability in bone structure and properties.

Grant Funding Source: Supported by US Department of Defense
Directed evolution toward inteins with alternative protein splicing mechanisms (566.2)
Authors: Cahn Sarah , Reitter Julie , Mills Kenneth
Published: June 2021

Protein splicing is a four‐step post‐translational event in which an intervening polypeptide, the intein, is removed and flanking polypeptides, the exteins, are ligated. We want to use directed evolution to discover inteins that splice by alternative mechanisms. The intein from Thermobifida fusca is similar in sequence to inteins that can bypass the first step of the protein splicing mechanism. However, the Thermobifida fusca intein requires this step. We want to create an intein that can bypass this step using selection systems that are based on intein‐dependent activity of thymidylate synthase or aminoglycoside‐phosphotransferase. We currently have tested a model system for the kanamycin‐resistance selection and are in the process of generating a pool of random mutants.

Grant Funding Source: This material is based upon work supported by the National Science Foundation under grant MCB‐124408
Investigating the roles of eIF4F and eIFiso4F in Arabidopsis thaliana (566.7)
Authors: Cole Nicola , Browning Karen
Published: June 2021

Eukaryotic initiation factor (eIF) 4F, the cap‐binding complex, binds to the messenger RNA (mRNA) in an early step in eukaryotic protein synthesis to recruit the mRNA to the protein making or translational machinery, the 40S ribosomal subunit. Higher plants such as Arabidopsis thaliana contain a plant‐specific cap‐binding complex, eIFiso4F, in addition to the conserved eIF4F complex found in eukaryotes. Genotypic and phenotypic differences between these complexes suggest functional differences. In an effort to define these functional differences, experiments performing RNA immunoprecipitation (RNA‐IP) using wild type Arabidopsis thaliana plant tissue, followed by deep sequencing, have been carried out to determine if there are different mRNA populations bound by the two different isoforms. Messages found to be differentially bound by one isoform over the other will be validated using other methods such as quantitative real time polymerase chain reaction (qRT‐PCR) and In vitro translation assays.

Grant Funding Source: Supported by NSF
Dimethylsulfide metabolism in marine isolates and their role in the biogeochemical cycling of sulfur (575.8)
Authors: Oduaran Erica
Published: June 2021

Microbial degradation is a major sink for dimethylsulfide (DMS), a volatile organosulfur compound which has been implicated in climate control and the biogeochemical cycling of sulfur. While the majority of marine bacteria which are capable of growth on DMS are members of the Methylophaga genus and belong to the Gammaproteobacteria class, recent studies have demonstrated that bacteria belonging to the Alphaproteobacteria class are also able to metabolize DMS. For example, a DMS monooxygenase, which carries out the first step in the DMS degradation pathway, was recently isolated from Hyphomicrobium sulfonivorans, the first enzyme of its kind to be isolated and characterized.1 The enzyme is a member of the flavin‐linked monooxygenases of the luciferase family and is most closely related to nitrilotriacetate monooxygenases. This work reports on the DMS monooxygenase activity of several bacteria isolated from Mount Hope Bay, RI.

Grant Funding Source: NSF
Molecular evolution of CYCLOIDEA in plant order Dipsacales (589.6)
Authors: Flatebo Charlotte , Berger Brent , Howarth Dianella
Published: June 2021

CYCLOIDEA (CYC) is a TCP transcription factor that has been shown to be involved in specifying dorsal identity in the petals of bilateral flowers. In the plant order Dipsacales, DNA sequencing has provided evidence that multiple, different functional copies of CYC have evolved, most likely via whole genome duplication events in the past. Previous studies of Dipsacales have generated gene trees for the various CYC copies; however, no one has tested if the different copies of CYC are under different selection pressures. Using several programs on the Datamonkey web server, we attempt to determine: (1) whether negative (purifying) selection, neutral evolution, or positive selection are acting on CYC; (2) are the different copies of CYC under different selective pressures; (3) is selection acting on the entire gene, certain amino acids or specific nucleotide sites; and (4) are shifts in selection detected following gene duplication and speciation.

Grant Funding Source: Supported by National Science Foundation
Discovery of small molecule hyperlipid accumulating triggers of algae Chlamydomonas reinhardtii identified via in vivo phenotype based screen (597.1)
Authors: Wase Nishikant , Boqiang Tu , Adamec Jiri , Cerny Ron , Black Paul , DiRusso Concetta
Published: June 2021

A large scale in vivo high throughput screen (HTS) was performed to identify small compounds that stimulate lipid production and accumulation using the model organism Chlamydomonas reinhardtii. The HTS employed a 384‐well microplate format in which cells were allowed to grow in the presence of the compounds at 10 μM final concentration for 72 hours. Accumulation of intracellular lipids was assessed using the lipophilic dye Nile Red and growth was monitored at OD600. The screening library included 43,736 compounds (ChemBridge, Corp). A total of 367 active compounds were identified that stimulated lipid accumulation to > 2.5‐fold and did not affect cell viability to give a hit rate of 0.8%. Primary hits were “cherry picked” and the sub‐set of compounds were retested using an 8‐point dose response assay (0.25‐30 µM). Hits were further assessed visually using a Nikon Ti‐inverted microscope (60X) to reconfirm lipid droplet accumulation was induced.. The final set of hits included 306 compounds. These were further compared for structural similarities using Tibco Spotfire Lead Discovery package and resulted in three main structural clusters: compounds with a piperazine, nitrobenzene, and/or adamantine group. The impact of the compounds on cellular metabolism was also characterization by quantifying Chl A, B, starch, protein and toxicity analysis. Currently, we are examining compound effectiveness in additional algal species such as Chlorella sorokiniana UTEX 1230, Tetrachlorella alterans UTEX 2453, C. protothecoides UTEX 29, C. vulgaris UTEX 395, Nannochloropsis sp.

Grant Funding Source: Supported by EPSCoR
Lipid‐dependent proliferation of breast and pancreatic cancer cell lines (605.7)
Authors: Pyrek Sebastian , Fahmi Tariq , Saeed Lamya , Biris Alex , Radominska‐Pandya Anna
Published: June 2021

Cancer cells rely heavily on anaerobic glycolysis for energy production, and have the capacity to synthesize their own sup¬ply of biologically active compounds of predominantly lipid origin. We hypothesize that any perturbation of this lipid pool, caused by drug treatment or changes in lipid metabolism, will result in significant alterations in the biological processes of these cells and result in cell death. In these studies, the lipid content of breast and pancreatic cell culture models has been assessed. Staining with Nile Red and Oil Red O indicate that primary cancer cell lines contain significantly higher lipid levels than metastatic lines and that the subcellular localization of these lipids also varies. Separation, identification, and quantitation of total lipid extracts by TLC and LCMS indicates that the proportions of phospholipids also vary in relation to the level of tumor cell differentiation. Treatment with drugs and transfection of cells with plasmids for specific UGT isoforms, which are known to conjugate various bioactive lipids and to be down regulated in several cancers, affects the lipid content and results in decreased cell proliferation and death. Nanodelivery of these drugs and plasmids significantly enhances these effects. Examining the role of lipids in cancer cell homeostasis is a novel approach to cancer research.

Grant Funding Source: Supported By DoD‐W81XWH1110795 and UAMS TRI ABCRP
A family 1 galactosyl hydrolase performs galactosyltransferase activity requiring Mg2+ and conferring freezing tolerance (617.8)
Authors: Roston Rebecca , Kuhn Leslie , Benning Christoph
Published: June 2021

The two most abundant photosynthetic thylakoid membrane lipids are monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG). Understanding galactolipid metabolism is therefore critical to understanding thylakoid formation and subsequent photosynthetic activity. The first enzymatic activity described to synthesize DGDG was named galactolipid: galactolipid galactosyl transferase (GGGT), as it removed a galactosyl head group from MGDG and transferred it to another MGDG making DGDG. Though it is now understood that a separate enzyme, DGD1, synthesizes most of the DGDG in vivo, GGGT was re‐identified in Arabidopsis as the gene product of SENSITIVE TO FREEZING 2 (SFR2). SFR2 was shown to protect Arabidopsis from freezing damage, to be located on the chloroplast outer envelope and to be similar to family‐1 β‐glycosidases. Here, we present a model of the 3‐dimensional structure of SFR2 based on its homology to family‐1 β‐glycosidases and show the functional significance of several unique regions. Using the model, we identify residues required for SFR2 activity that are not conserved among family‐1 β‐glycosidases. We experimentally define pH and temperature optimums for enzymatic activity in vitro. Unexpectedly, we show that SFR2 is a metalloenzyme, unlike its family members. Our data suggest that while SFR2 retains the core structure and active site residues of a family‐1 β‐glycosidase, it has unique residues, regions, and co‐factors required to alter its function to that of a transferase.

Grant Funding Source: Supported by the Department of Energy
Using biochemistry and molecular biology alignment tables to improve assessment and outcomes (618.17)
Authors: Sensibaugh Cheryl , Caldwell Ben , Provost Joseph , Bell Ellis
Published: June 2021

The ASBMB has begun the next phase of the Research Coordination Networks in the Undergraduate Biology Education (RCN UBE) project funded by the National Science Foundation. The goal of the RCN UBE is to support groups of investigators and educators to provide opportunities to foster new collaborations focusing on ways to improve participation, learning or assessment in undergraduate biology curriculum. November, 2013 the ASBMB hosted its first in a series of meetings to implementing concept‐driven teaching strategies to implement the overarching goals of AAAS’ “Vision and Change” with the RCN UBE meeting. The goal of the meeting, held at the Chemistry and Biochemistry department of the University of San Diego was to create a scientific teaching took kit for biochemistry and molecular biology educators. Participants were introduced to the core concepts/BMB foundations developed by the BMB community, assessment and how to take a scholarly approach to teaching. Faculty, post‐docs and graduate students from a diverse set of institutions were then guided to craft specific learning goals and objectives that included assessment mechanism and teaching strategies using a careful and stepwise approach. The learning goals and assessments were created using the biochemistry and molecular biology foundational core concepts defined by the BMB community with the ASBMB. Each group’s “toolkit” of goals, objectives and methods to assess these foundational concepts were shared with the entire group and will be available to the BMB community as additional workshops create more items. Work funded by NSF Grant 0957205 to EB

Grant Funding Source: NSF
Data‐driven assessment techniques to catalyze student learning (618.19)
Authors: Offerdahl Erika
Published: June 2021

As we rearticulate the undergraduate biochemistry curriculum to emphasize deep foundations in core biochemical principles and skills, we must also reconsider the assessment of student learning. Assessment is perhaps an instructor’s most powerful tool for affecting student learning, particularly when it is used to diagnose student understanding and to subsequently adjust activities to address learning difficulties. Yet, in undergraduate science teaching, assessment is largely employed as a summative activity, reducing its effectiveness as a tool for developing student understanding. While extensive research at the K‐12 level provides several insights into best practices for assessment, there is less research at the undergraduate level in general, and undergraduate science in particular.

The purpose of the research presented here is to contribute to the growing literature base on effective assessments for undergraduate learning in the molecular life sciences. We designed and tested the efficacy of two formative assessment tools in large‐enrollment, introductory biochemistry courses for majors. Both tools make use of Learning Management Systems (e.g. Desire2Learn, Blackboard, WebCT) to formatively assess and diagnose student understanding and provide responsive feedback for instructors and students to inform learning. Data collected for analysis include: student clickstream data from Learning Management System usage, student open‐response items, student achievement data, and self‐report data. We will present results demonstrating the effectiveness of these tools in terms of (1) ability to uncover the range and extent of student reasoning difficulties, (2) ease and use by instructors, (3) utility to predict student performance and enact early warning systems for at‐risk students, and (4) impact on student learning.

Grant Funding Source: Supported by the National Science Foundation, HRD‐0811239
A church‐based, diet and supervised physical activity behavioral intervention for rural, southern African American adults improves diet and physical activity‐related psychosocial constructs (624.1)
Authors: Thomson Jessica , Tussing‐Humphreys Lisa
Published: June 2021

Obesity and its comorbidities, including cardiovascular disease, hypertension, and diabetes, are largely preventable or modifiable through behavioral factors, such as diet and physical activity (PA). We examined post intervention changes in psychosocial constructs of behavioral change [decisional balance (pro and con), self‐efficacy, and social support] related to fruit, vegetables, whole grains, sugar‐sweetened beverages (SSB), and PA. Data are from 409 participants enrolled in a 6‐month, church‐based, diet and supervised PA intervention conducted in a rural, southern, African American population. Group differences were assessed using mixed model regression analysis. Separate analyses revealed significant diet quality improvements for fruit, vegetables, and discretionary calories (as measured by the Healthy Eating Index‐2005), and increased PA in the intervention group. The present analyses revealed significant increases in all 5 social support scales for the intervention group, with only fruit and vegetable scale increases for the control group. Self‐efficacy for SSB increased in both groups, while decisional balance (pro) for whole grains increased only in the control group. Results indicate that social support may be a more important mediator of behavioral change for diet and PA than decisional balance or self‐efficacy in this population of rural, southern, African American adults.

Grant Funding Source: Supported by US DHHS HRSA Grant # 6 U1FRH07411and the USDA Agricultural Research Service.
CALERIE II: the effect of 25% calorie restriction over two years on cognitive function (629.7)
Authors: Scott Tammy , Das Sai , Martin Corby , Stewart Tiffany , Williamson Donald , Stein Rick , Bhapkar Manjushri , Pieper Carl , Rochon James , Roberts Susan
Published: June 2021

Calorie restriction (CR) extends lifespan in a range of animal models and potentially decreases disease risk factors in humans. It is unclear, however, how CR impacts cognition; a negative outcome could decrease the feasibility and practicality of CR for health improvement. Previous studies in both animal models and humans have provided inconsistent findings reporting either positive, negative, or no effects. Our objective was to study the effect of CR on cognition during a 2‐year, multi‐center, randomized controlled trial. The analysis population was comprised of 218 healthy normal‐ and over‐weight adult volunteers who were enrolled into the CALERIE study, were randomized 2:1 into a 25% CR or an Ad Libitum control group, and began intervention. Cognition was measured through a computerized battery of tests (reaction time, attention/vigilance, verbal and visual memory, working memory, and executive function) at baseline, and 6‐, 12‐, and 24‐month follow‐up. Analysis was on an intention‐to‐treat basis, with models adjusted for study site, sex, baseline BMI stratum (18.5 ‐ 24.9 kg/m2 and 25 ‐ 28.9 kg/m2), baseline scores, age and education. Our results showed no consistent main effect of study intervention for any of the cognitive tests, nor a significant interaction between intervention and BMI stratum. Our null findings suggest that cognitive outcome is not a limitation for the use of CR for health improvement.

Grant Funding Source: Supported by: USDA agreement No. 58‐1950‐0‐014 and NIA grant No. U01AG022132