bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Buzz Off” Zika
Authors: Grant Fran , Arendt N. , Ducheny K. , Norton M. , Ovsepyan T. , Ruege M. , Wildermuth H. , Silvaggi Nicholas 
Published: November 2023

Zika virus, or ZIKV, a mosquito‐borne pathogen, is a current public health concern due to its link to microcephaly and Guillain‐Barré syndrome. A flavivirus, ZIKV contains an RNA genome translated using the host cell's protein synthesis machinery. The 5′ end of the viral RNA possesses a “cap” of methylated bases that protect it from being destroyed by the host's immune system. This cap is produced by a virally‐encoded methyltransferase enzyme, the NS5 methyltransferase (MTase). Since the 5′‐RNA cap is required for viral reproduction, inactivating the NS5 MTase with a small molecule inhibitor should be a viable treatment for ZIKV infections. The NS5 MTase transfers CH3 groups from the ubiquitous methyl donor molecule S‐adenosylmethionine (SAM) to specific positions on bases at the 5′ end of the viral RNA. Based on the binding mode of SAM observed in a crystal structure (5KQR), an analog of SAM was developed that could inhibit the enzymatic activity of the MTase. SAM binds in a pocket composed of Ser56, Arg84, Trp87, Thr104, Lys105, His110, Glu111, Asp131, Val132, Phe133, Asp146, and Ile147. The Grafton SMART (Students Modeling A Research Topic) Team has modeled the NS5 MTase with either SAM or the hypothetical inhibitor MO2 bound using 3D printing technology. Models with such compounds bound to the enzyme provide information that might help increase the potency of potential inhibitors and improve their selectivity for the ZIKV MTase.Support or Funding InformationThis work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).
RPE65 – Essential Visual Cycle Protein
Authors: Kaiser Carl , Ahn P. , Arnhold K. , Bartos S. , Burkle B. , Chang M. , Coury M. , Cowan N. , Dittrich N. , Foster R. , French J. , Gamblin T. , Gorski J. , Hameed M. , Homberg L. , Johnson R. , Khan S. , Lewis E. , Otten J. , Rivera M. , Sabatino A. , Sargent T. , Schimmels J. , Smith A. , Stegeman R. , Strom D. , Strom J. , Tsuji B. , Visaya C. , Yamat J. , Yorke N. , Klestinski Keith , Huckenpahler Alison 
Published: November 2023

Leber congenital amaurosis (LCA) is a genetic disease associated with blindness that is caused by mutations in retinal pigment epithelium (RPE65), an enzyme involved in the visual cycle. When light hits photosensitive pigments in the retina, it conformationally changes 11‐cis‐retinol (a form of vitamin A) to 11‐trans‐retinol. This conversion allows for a series of chemical reactions and the formation of electrical signals that communicate with the brain. RPE65 is essential to the cycle because it changes 11‐trans‐retinol back into 11‐cis‐retinol‐‐recycling the enzyme and allowing for sustained vision[1] . The Marquette High SMART (Students Modeling A Research Topic) Team used 3D printing technology to model how mutations in LCA affect RPE65's structure and function. RPE65 has 533 amino acids folded into sheets that arrange themselves into seven propeller blades, which collectively create a mostly hydrophilic tertiary structure. One face of RPE65 is hydrophobic and is associated with the microsomal membrane. A hydrophobic, tunnel‐like structure leads to an iron cofactor that facilitates its enzymatic efficiency. The iron cofactor is held in the active site by the histidine residues H180, H241, H417, and H527 in a coordinated motif. Mutations near the active site cause lowered enzymatic activity and LCA. Other residues that are commonly mutated in LCA include Gly40, Arg91, Glu102, Arg124, His182, and Val473. Ocular imaging data has shown phenotypic changes in the photoreceptors in patients with RPE65 mutations. With novel gene delivery methods and other treatment strategies, these technologies will be useful to understanding how to treat LCA and other retinal diseases. [2]Support or Funding InformationThis work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).
Inhibition of δ‐Opioid Receptors
Authors: Krukar Paula , Burmeister Katrina , Davis Evan , Dragseth Luke , Gent Austin , Janssen Andrew , Koch Stephen , Shaheer Mohammad , Panta Shadika , Brown Katie , Cunningham Christopher W. 
Published: November 2023

Opioid addiction and abuse affects between 26 and 36 million people worldwide (Volkow, 2014), prompting researchers to try to design a drug that both has painkilling effects but does not create a dependency. Most opioid analgesics work through activation of mu opioid receptors (MOR). They naturally bind to opioid peptides, such as endomorphins 1 and 2, in order to regulate pain. Another important target is the delta opioid receptor (DOR). Inhibition of DOR has been shown to slow the development of addiction to MOR agonists in animal models of pain. DOR are proteins that transpermeate the cell membrane with seven alpha helices. Schiller and colleagues first reported an endomorphin analogue, DIPP‐NH2, that activates MOR and also inhibits DOR. DIPP‐NH2 is structurally similar to the natural endomorphins, so it can bind DOR through similar mechanisms. The DIPP‐NH2 interacts with the Met132, Tyr129, Val217, Ile277, and Trp284 on DOR. Moreover, one of the two methyl groups on DIPP‐NH2 engages Val281 and Ile277. Finally, a salt bridge forms between the DIPP‐NH2 N‐terminus and Asp128, and this salt bridge is crucial for opioid receptor ligand recognition. The Whitefish Bay High School SMART team (Students Modeling a Research Topic) is modeling DOR using 3D printing technology. DIPP‐NH2 may be the basis of a non‐addictive painkiller, which would be a significant advancement toward alleviating the major societal and financial problem of opioid addiction.Support or Funding InformationThis work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).
NMDAR Helps You Think, So Please Reconsider That Extra Drink
Authors: Sampe David , Block Gavin , Davis TJ , Dong Nancy , Freuler Jonah , Mietkowski Mitchell , Rowney Toni Jo , Stoehr Noel , Peoples Robert W. 
Published: November 2023

According to the U.S. Centers for Disease Control and Prevention, each year 88,000 people die from alcohol‐related causes in the United States. Ethanol misuse, a deadly and expensive societal problem, cost the United States $249 billion in 2010 (1). Ethanol targets many proteins in the brain. Specifically, it acts as an inhibitor of the N‐Methyl‐D‐aspartate receptor (NMDAR), which mediates much of the excitatory synaptic transmission in the brain. Normally, the NMDAR is activated when glutamic acid binds to it allowing positive ions to flow through the cell membrane; this facilitates learning and memory in the brain. However, ethanol inhibits the activity of the NMDAR, interfering with synaptic transmission. A type of glutamate ion channel receptor found in neurons, NMDAR, has four domains: the amino terminal domain, the ligand binding domain, the membrane‐associated (M) domains, and the carboxy terminal domain. NMDAR is a heterotetrameric protein with two GluN1 and two GluN2 subunits. Ethanol interacts with NMDAR in the M domains with specific amino acids including Gly638 in the GluN1 subunit as well as Phe637 and Gly826 in the GluN2B subunit (2,3). Researchers are determining the location of the strongest NMDAR‐ethanol interactions using amino acid substitutions. The Brown Deer High School SMART (Students Modeling A Research Topic) Team has designed a model of NMDAR using 3D printing technology to visualize the NMDAR‐ethanol interactions. If researchers can develop molecules to help minimize the effect of ethanol on the brain, it could reduce the cost of alcoholism to society.Support or Funding InformationThis work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).
Coughing up a Cure for Whooping Cough with Pertussis Toxin
Authors: Tiffany Karen , Arnholt A. , Arnholt S. , Arzumanyan D. , Arzumanyan L. , Butt A. , Houghtaling A. , Ketelhohn L. , Levy J. , Miller N. , Minerva N. , Remington E. , Tiffany B. , Wankowski J. , Barbieri Joseph , Zuverink Madison 
Published: November 2023

The CDC reported 32,971 cases of pertussis, or whooping cough, in 2014. This respiratory infection mainly affects unvaccinated infants and toddlers, and symptoms include paroxysmal coughing with whooping, vomiting, and pulmonary complications which can lead to death. Pertussis toxin (PT), produced by the pathogenic bacteria Bordetella pertussis, causes whooping cough by ADP‐ribosylating the Gi protein that inactivates adenylyl cyclase. The inactive ADP‐ribosylated Gi protein is unable to interact with G protein‐coupled receptors, leading to an increased intracellular concentration of cAMP. Increased concentrations of cAMP can interfere with normal cell signaling, disrupting specific cellular functions. PT is a critical virulence factor for B. pertussis that also has potential to create human immunity against pertussis. The Cedarburg SMART Team (Students Modeling A Research Topic) modeled PT using 3‐D printing technology to study structure‐function relationships. PT contains a total of six subunits, four individual subunits (S1, S2, S3, and S5) and a pair of identical subunits (S4). The A domain consists of the S1 subunit, the catalytic portion of the toxin. Mutations in Glu129 and His35 can reduce ADP‐ribosyltransferase activity. Mutations in Arg9, Asp11, and Arg13 also reduce catalytic activity. Trp26 interacts with NAD+, an important cofactor. The B domain, responsible for binding to cell receptors, contains the remaining subunits. Effective vaccines contain chemically‐inactivated PT. However, whole cell pertussis vaccine may cause severe side effects, while acellular pertussis vaccine is not as potent. Non‐toxic derivatives of pertussis toxin may be engineered, improving the potency of the acellular vaccine without harmful side effects.Support or Funding InformationThis work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).
Evaluation of a Reduced Sampling Schedule for Assessment of Pancreatic Beta‐Cell Function with the Intravenous Glucose Tolerance Test During a Dietary Intervention
Authors: Palacios Orsolya M , Nieman Kristin M , Cook Chad M , Maki Kevin C 
Published: November 2023

Pancreatic beta‐cell function is a key determinant of glucose tolerance. The intravenous glucose tolerance test (IVGTT) can be used to assess both the insulin sensitivity index (Si) and the acute insulin response to glucose (AIRg). The disposition index (DI = Si × AIRg) reflects the adequacy of pancreatic beta‐cell response for the level of insulin sensitivity. The aim of this analysis was to compare the AIRg and DI values calculated using a reduced early test sampling schedule (t = 0, 5, 10 min), to those from the full sampling schedule (t = 0, 3, 5, 7, and 10 min). Participants included men (n = 8) and women (n = 16) with mean (SD) age 48.9 (9.9) y and body mass index 30.8 (4.9) kg/m2. Subjects consumed 0, 15, and 30 g/d high‐amylose resistant starch (RS) for 4 weeks each, in a double‐blind, randomized, crossover trial, and underwent a 180‐min IVGTT at the end of each treatment period. The Minmod Millenium program was used to derive Si. AIRg was calculated as the mean increment in plasma insulin during the first 10 min of the test for the full and reduced sampling schedules. The median (interquartile range) full schedule AIRg values during the control, 15, and 30 g/d RS conditions were 43 (29, 103), 47 (23, 67) and 44 (30, 94) mU/L, respectively. Mean (95% confidence interval) percentages of the full schedule values for the reduced schedule values were 82 (79–86), 87 (76–98) and 83 (80–85) for the control, 15 and 30 g/d RS conditions, respectively, all p < 0.05 vs. the full schedule. Correlations between the AIRg and DI values from the two schedules during each RS condition were high (Pearson r values all ≥0.98, p < 0.001). Thus, although AIRg and DI values cannot be directly compared between sampling schedules, the reduced sampling schedule accurately reflects relative AIRg and DI values, and may thus be a time and cost‐effective option when conducting the IVGTT in clinical and epidemiological studies.Support or Funding InformationIngredion Inc., Westchester, IL
Consumption of Bifidobacterium animalis subsp. lactis BB‐12 reduces TNF‐α secretion from LPS‐stimulated PBMCs, but does not alter serum TNF‐α levels
Authors: VanEvery Hannah Leigh , Meng Huicui , Flemming Jennifer A , Lee Yujin , Ba Zhaoyong , Furumoto Emily J , Roberts Robert F , Kris‐Etherton Penny M , Rogers Connie J 
Published: November 2023

Increasing evidence suggests that probiotic bacteria can modulate inflammatory responses. However the immune response varies by species and strain of organism, as well as delivery matrix of the probiotic. Furthermore the tissue compartment and assay method by which inflammatory mediators are quantified in clinical trials is a debated issue. The goal of the current study was to evaluate the effect of one probiotic species, Bifidobacterium animalis subsp. lactis BB‐12 at a dose of log 10 ± 0.5 CFUs/day on both plasma‐ and in vitro cultured peripheral blood mononuclear cells (PBMC)‐derived inflammatory mediators in a partially blinded, 4‐period crossover, free‐living study. Healthy adults (n=30) aged 18–40 years were recruited, and received 4 treatments in a random order: 1) yogurt smoothie alone; smoothie with organism added 2) before or 3) after fermentation, or 4) organism given in capsule form. At baseline and after each treatment, plasma was collected and PBMCs were isolated and stimulated in vitro with LPS as an inflammatory stimulus. Inflammatory cytokines were quantified in each compartment at baseline and after each treatment. Participants who consumed yogurt smoothies with BB‐12 added post‐ fermentation had a significant reduction in TNF‐α secretion from LPS‐stimulated PBMCs compared to baseline (p=0.039). However, there was no treatment effect observed in plasma TNF‐α levels. Additionally, plasma TNF‐α levels were not correlated with TNF‐α produced by cultured PBMCs in the presence of stimulation. These results demonstrate that quantification of inflammatory mediators in the plasma of healthy adults may not be adequate to detect the effect of probiotic consumption on inflammatory responses. The assessment of a nutritional intervention on in vitro cultured PBMCs in response to LPS stimulation may be a more sensitive assay method to detect probiotic‐induced changes in inflammatory responses. These findings demonstrate that selection of the tissue compartment and the assay method to evaluate inflammatory response is a critical variable in clinical trial design.Support or Funding InformationDairy Research Institute
Estimation of Growth Model Parameters for Mini Pig Breeds
Authors: Jo Hyunwoong , Lee Sang Chul , Kim Dae Cheol , Kim Beob Gyun 
Published: November 2023

Pigs are used as models for human because of the similarities in digestive systems. Mini pigs are often used in nutritional studies as well as organ transplantation studies. The relatively small pigs are easier to handle than large pigs. An accurate estimation of body weight of mini pigs is important in animal experimentation. The objective of this work was develop growth models for two mini pig breeds: a M‐Pig® breed originating from Korean Jeju Island native pigs (Cronex Co., Ltd., Hwaseong, Republic of Korea) and Micro‐pig® (Medi Kinetics Co., Ltd., Pyeongteak, Republic of Korea). The M‐Pig® is developed by selecting Jeju Island native pigs with slow growth rate for the purpose of human organ transplantation research. A total 680 body weight data ranging from 0.8 to 63.2 kg for 40 animals were collected from birth to 52 weeks of age. The Micro‐pig® is a crossbreed developed by breeding white gilts selected from cross breeds (Korean native pig, Yucatan mini pig, Vietnamese pot‐bellied pig, and Pygmy pig) with Meishan boars. A total of 36 body weight and age data (mean values of 128 animals) ranging from 0.35 to 33.5 kg and 0 to 96 weeks, respectively, were obtained from 20 published experiments and Medi Kinetics (Pyeongtaek, Republic of Korea). Two different nonlinear growth models with 3 parameters in the equation were employed. Estimated body weight growth models of M‐Pig® as a function of age (week) were: body weight, kg = 64.57 × e−3.21×e^‐0.06t with R2 = 0.976 in Gompertz model and body weight, kg = 57.94 × (1 + 12.33 × e−0.11t)−1 with R2 = 0.969 in Logistic model. Estimated body weight growth models of Micro‐pig as a function of age (week) were: body weight, kg = 31.47 × e−2.10×e^‐0.07t with R2 = 0.793 in Compertz model and body weight, kg = 30.45 × (1 + 4.76 × e−0.10t)−1 with R2 = 0.775 in Logistic model. The age at point of inflection in Gompertz model showed that the maximum growth rate of M‐Pig® and Micro‐pig® was at 18.9 and 11.2 weeks of age, respectively. The body weight at inflection in Gompertz model of M‐Pig® and Micro‐pig® was 23.8 and 11.6 kg, respectively. Taken together, Gompertz models resulted in greater fitness to the growth curve of mini pigs compared with Logistic models. Suggested growth curves for mini pigs may be used for the estimation of body weight gain. Further research is warranted to refine the growth models for mini pigs with a greater amount of data.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2016R1A2B2015665).
The Association of Cord Blood 25(OH)D Levels with Neonatal Body Size and Composition: The Healthy Start Study
Authors: Koeppen Hallie J , Kalata Kathryn , Stamatoiu Alexandra V , Ringham Brandy M , Glueck Deborah H , Norris Jill M , Dabelea Dana , Sauder Katherine A 
Published: November 2023

Micronutrient deficiencies during pregnancy are associated with an increased risk of chronic disease in offspring. There is some evidence that vitamin D deficiency in pregnancy is associated with increased offspring adiposity, but evidence from human studies is inconclusive. We examined associations of vitamin D (25‐hydroxyvitamin D [25(OH)D]) in cord blood with neonatal size and body composition in 600 mother‐infant dyads from the Healthy Start study, an ongoing, pre‐birth prospective cohort study in Denver, Colorado. Total 25(OH)D (nmol/L) was measured in cord blood serum collected at delivery (39.6±1.1 weeks gestation). Weight‐for‐gestational‐age z‐scores (WGAZ) were calculated from birth weight (g) and birth length (cm) measured at delivery. Neonatal fat mass (g) and fat‐free mass (g) were measured (median 1 day post‐birth) via air displacement plethysmography (PEA POD). We used multivariable linear regression to examine the association of cord blood 25(OH)D with neonatal outcomes, adjusting for maternal age, education, income, race/ethnicity, pre‐pregnant BMI, prenatal smoking, prenatal physical activity, gestational diabetes, gestational weight gain, offspring gestational age at birth, season of birth, and infant sex. We also evaluated effect modification by maternal race/ethnicity and pre‐pregnant BMI. We observed interactions of total 25(OH)D with race/ethnicity for the outcome of offspring birth weight and with maternal pre‐pregnant BMI for the outcomes of offspring birth weight and fat mass (p<0.05 for all interaction terms). The association between birth weight and 25(OH)D was modified by race (p=0.04). The largest effect was observed in Hispanic participants (β= −103.8 grams per 1 nmol/L increase in 25(OH)D, p=0.003) with smaller effects observed among non‐Hispanic white (β= −55.8g, p=0.03), non‐Hispanic black (β= −44.4g, p=0.21), and other (β= −44.4g, p= 0.28) offspring. Associations of total 25(OH)D with birth weight (p=0.02) and fat mass (p=0.04) also differed by maternal pre‐pregnant BMI. Each kg/m2 increase in pre‐pregnant BMI increased the magnitude of the association between 25(OH)D and birth weight by 0.24g per nmol/L 25(OH)D (p=0.02) and between 25(OH)D and fat mass by 0.08g per nmol/L 25(OH)D (p=0.04). Total 25(OH)D was not associated with offspring birth length (p=0.59), fat‐free mass (p=0.61), or WGAZ (p=0.79). In conclusion, we found that total cord blood 25(OH)D is associated with neonatal size and body composition, although the strength and direction of these associations differ according to maternal race/ethnicity and pre‐pregnant BMI. Further research is needed to understand the implications of these associations as infants grow.Support or Funding InformationSupported by the National Institutes of Health and the American Heart Association
Vitamin D, Calcium Intakes, Physical Activity and Association with Bone Mineral Content Among Adolescents in Malaysia
Authors: Majid Hazreen Abdul Abdul , Aziz Suriawati Abu , Sadat Nabilla Al , Su Tin Tin , Mohd Nahar Azmi , Jalaludin Muhammad Yazid 
Published: November 2023

BackgroundDietary calcium, vitamin D and physical activity play significant roles in bone development especially throughout children and adolescent growth period. Calcium needs during adolescence increases and the intake of vitamin D may have influence on the BMC.Learning OutcomeDietary vitamin D and calcium intake, physical activity (score) and bone mineral content (BMC) among Malaysian adolescents.ObjectiveThe objective of this study was to determine the dietary intake of vitamin D, calcium and physical activity level with BMC among 13‐year old school‐going Malaysian adolescents.MethodA cross‐sectional from the Malaysian Health and Adolescents Longitudinal Research Team Cohort Study (MyHeARTs) were conducted among 13‐year old participants of schoolchildren attending Secondary One from central region that includes Kuala Lumpur, Selangor and Perak. The study used a stratified sampling design to select the study participants. Seven‐day diet history were done by trained dietitians and the data were analysed using Nutritionist Pro, using local food database and Singapore Energy and Composition of Food database. BMC of the calcaneus was measured using portable broadband ultrasound bone densitometer (Hologic Sahara, Hologic Inc., USA) as part of the evaluation.ResultsA total of 289 adolescents (65.7% females) were recruited. All subjects had lower intake of vitamin D in comparison with the Recommended Nutrient Intake of Malaysia, 5 μg/day with the mean of 2.51 ± 0.12 μg/day (2.55 ± 0.23 μg/day in male and 2.50 ± 0.14 μg/day in female). Urban adolescents took more food that contained vitamin D than rural counterpart 2.52 ± 0.14 vs 2.46 ± 0.13 μg/day. The average dietary intakes of calcium were 377 ± 12 mg/day (380 ± 14 in urban vs 358 ± 14 mg/day in rural counterpart), respectively, with the majority of subjects failing to meet the Recommended Nutrient Intake (RNI) of Malaysia for dietary calcium of 1000 mg/day. A significant positive relation to BMC was found for dietary vitamin D and calcium intake. All the subjects had a normal Z‐score for the BMC (−2.00 or higher) with a mean of 0.55 ± 0.01 (0.55 ± 0.01 in urban vs 0.54 ± 0.01 mg/day in urban counterpart). Average physical activity score for the participants was categorised as inactive (2.01 ± 0.03).ConclusionsThis study highlights that Malaysian adolescents had inadequate dietary vitamin D and calcium intake and there was no difference between those living in urban or rural. A combination of adequate vitamin D and calcium intake showed positive BMC. It is crucial to promote active lifestyle messages to this age group.Support or Funding InformationFunding Disclosure: Supported by grants from University of Malaya Research Programme (RP022A,C‐14HTM) and UMSC fund cycle 1‐2016.