bluuebunny/crossref_metadata_2025 huggingface dataset:
Black soybean may be effective to recover the impaired insulin signaling in high cholesterol diet induced non‐alcoholic fatty liver disease mice model
Authors: Jung Ji‐Hye , Yoon Lee‐Na , Kim Hyun‐Sook
Published: June 2021

NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat more than 5% per liver weight. In this study, we investigated the effects of low and high concentrations of black soybean on the insulin signaling of mice fed high‐cholesterol diets. Mice were randomly allocated into 5 groups that were fed different diets: the normal cholesterol diets (NCD); high‐cholesterol diets (HCD); and HCD with 1%, and 4% black soybean powder (1B‐HCD, and 4B‐HCD, respectively). Blood glucose and insulin were significantly lower in the black soybean‐supplemented groups (129.2mg/dl, 1.76μIU/ml; 113.7mg/dl, 2.29μ IU/ml) than that in the HCD group (163.2mg/dl, 3.07μIU/ml). The serum HOMA‐IR and free fatty acid concentration were significantly higher in the HCD group than in the NCD, and it was decreased by black soybean supplementation. We measured adiponectin as it is critical adipokine involved in insulin resistance in NAFLD. The adiponectin was significantly lower in the HCD group than that in the NCD and significantly increased with black soybean supplementation. These results suggest that the black soybean restores the fasting glucose via adiponectin secretion.

Grant Funding Source: ASN
Date seed powder‐containing bread exhibits higher levels of flavonoids and antioxidant capacity compared to regular and whole wheat bread
Authors: Platat Carine , Habib Hosam M , Ibrahim Wissam H , Hashim Isameldin Bashir , Eldin Afaf Kamal
Published: June 2021

Date fruit seeds have been identified as an excellent source of antioxidants that contribute to reduced risk of chronic diseases. Arabic bread, which is wheat flour‐based, is a major staple food in the Arab World. Higher antioxidant content has been observed in date seed powder compared to wheat and whole wheat flour. In the present study, date seed was used as a functional food ingredient to develop Arabic bread with potentially enhanced antioxidant capacity through replacement of wheat flour with different levels of date seed powder (5, 10, 15 and 20%). Regular and whole wheat Arabic breads were used as controls. Total flavonoids, total phenolics, antioxidant capacity, protein, fat, fiber, and moisture were determined. Nutritional properties were similar among controls, 5%, 10%, and 15% date seed powder bread. Bread with 20% date seed powder had significantly higher amounts of fiber and fat compared to others. Total flavonoids and antioxidant capacity increased in date seed powder bread in a dose‐dependent manner. A significantly higher content of total flavonoids was observed in 10%, 15%, and 20% date seed powder bread compared to controls. Antioxidant capacity was significantly higher in date seed powder bread compared to controls, even at 5%. These results demonstrate that date seed powder‐containing bread exhibits higher levels of flavonoids and antioxidant capacity compared to regular and whole wheat bread.
FADS genotype affects change in fatty acid levels after a Mediterranean dietary intervention
Authors: Djuric Zora , Porenta Shannon , Ren Jianwei , Ko Yi‐An , Baylin Ana , Mukherjee Bhramar , Gruber Stephen
Published: June 2021

A Mediterranean diet increases intake of n‐3 and n‐9 fatty acids and lowers intake of n‐6 fatty acids. Limiting n‐6 fatty acid levels is expected to decrease levels of pro‐inflammatory eicosanoids such as prostaglandin E2 (PGE2) that increase colon cancer risk. This study evaluated whether polymorphisms in fatty acid desaturases (FADS1 and FADS2) genes may identify subgroups that have a greater response to dietary changes. A total of 107 individuals with a personal history of adenomas or colon cancer were randomized to either a Mediterranean diet or a Healthy diet. Fatty acids were measured in both serum and colonic mucosa at baseline and at 6 months. Each individual was genotyped for 4 SNPs in the FADS1/FADS2 cluster. Genetic variation in the FADS cluster was strongly associated with baseline serum arachidonic acid (p<0.0001) but less evidence was present for serum and colonic mucosa n3 fatty acids. Minor allele carriers had lower 20:4, n6 levels at baseline than major allele carriers. Both diets led to slightly but not significantly lower 20:4, n6 levels at 6 months. The Mediterranean diet intervention increased long chain n3 fatty acids in the colonic mucosa. There was a significant interaction of diet and FADS genotype on changes in fatty acid levels after intervention indicating that a Mediterranean intervention may have a relatively larger impact in specific subgroups.
Striatal development involves a switch in gene expression networks, followed by a myelination event: implications for neuropsychiatric disease
Authors: Novak Gabriela , Fan Theresa , O'Dowd Brian F , George Susan R
Published: June 2021

Abnormal development of striatal neurons is thought to be part of the pathology underlying psychiatric illness. We studied striatal gene expression patterns during an active striatal maturation period, the first two postnatal weeks in the rat. This parallels human striatal development during the second trimester, when prenatal stress is thought to lead to increased risk for neuropsychiatric disorders. Using subtractive hybridization and quantitative real‐time PCR, we characterize the developmental expression of more than 60 genes, many not previously known to play a role in neuromaturation. We show that during the first two postnatal weeks in the rat, an early gene expression network that lacks key striatal‐specific signaling pathways is downregulated and replaced by a mature gene expression network, containing key striatal‐specific genes, which confer functional identity to these neurons. Hence, early postnatal striatal neurons lack many of their key characteristics. This maturation process is followed by a rise in the expression of myelination genes, indicating a striatal‐specific myelination event. This strictly controlled developmental program is likely to be susceptible to disruption by external factors. Alterations in its normal progression may play a role in the etiology of neuropsychiatric disease. Indeed, this period is known to be a susceptibility period in both humans and rats.
Differential effect of mesenchymal stem cell therapy on cardiac glucose utilization in the infarcted heart following chow and high fat feeding
Authors: Hughey Curtis , Ma Lianli , James Freyja D , Bracy Deanna P , Wasserman David H , Rottman Jeffrey N , Shearer Jane
Published: June 2021

OBJECTIVE

To determine whether mesenchymal stem cell therapy minimizes abnormal cardiac glucose utilization following a myocardial infarction (MI) in the presence of dietary‐induced insulin resistance.

METHODS

C57BL6 mice were high fat‐fed (HFF) for eight weeks. Mice were separated into three groups: HFF‐SHAM, HFF‐MI+PBS in which mice were given a MI followed by intramyocardial injection of saline and the HFF‐MI+ MSC group receiving MSCs. HFF groups were age‐matched with chow‐fed mice.

RESULTS

Five weeks post‐MI, cardiac glucose utilization was evaluated in the conscious, unrestrained mouse by performing a hyperinsulinemic‐euglycemic (insulin) clamp coupled with [14C]‐2‐deoxyglucose administration. In chow‐fed mice, MSCs preserved glucose uptake (μg/mg/min) in the remote left ventricle (RLV) (7.36 vs. 5.16 vs 6.00; CHOWSHAM vs CHOW‐MI+PBS vs CHOW‐MI+MSC). In HFF mice, MSCs increased insulin‐stimulated glucose uptake in the periinfarct region (3.85 vs 3.84 vs 5.24; HFF‐SHAM vs HFF‐MI+ MSC vs HFF‐MI+MSC). RLV glucose uptake in the HFF‐MI+ MSC group was higher than that of the HFF‐MI+PBS mice (4.80 vs 3.38). Immunoblots indicate MSCs preserve insulin signaling (p‐Akt/Akt) in chow‐fed mice. In contrast, this ratio was similar in HFF groups.

CONCLUSIONS

MSC tberapy promotes insulin sensitivity post‐MI differently in response to a high fat diet. Funded by CIHR and Killam Trusts.
Human milk oligosaccharides reduce EPEC attachment in vitro and EPEC colonization in mice
Authors: Manthey Carolin Friederike , Autran Chloe , Eckmann Lars , Bode Lars
Published: June 2021

Breastfeeding is associated with a lower risk for enteric infections, in part due to human milk oligosaccharides (HMO), unconjugated complex glycans that are present in human milk (5–15g/L), but not in infant formula. Enteropathogenic Escherichia coli (EPEC) are attaching/effacing pathogens that can cause enteric infections and serious diarrheal illness with potentially high mortality in infants, especially in developing countries. Our objective was to assess whether HMO reduce EPEC attachment in vitro and colonization in vivo.

Physiological concentrations of HMO (10g/L) reduced EPEC attachment to cultured epithelial cells (HeLa and T84) by 99% compared to mock‐treated controls (p<0.0001). Galactooligosaccharides (GOS, 8g/L), currently added to infant formula, had no effect. In 7‐day old suckling mice, oral administration of HMO (15mg/d) thrice daily the day prior and after EPEC exposure reduced colon EPEC counts to 3.8E+06 compared to 1.1E+08 in PBS‐treated littermates (p=0.015) and 5.1E+08 in GOS‐treated littermates.

Our data suggest that HMO reduce EPEC attachment in vitro and colon colonization in suckling mice. We now aim to identify which of the more than 130 different HMO contribute to the observed effects and whether our results translate to human infants.
Cholesterol‐induced inflammation on adipose tissue is reduced by a carbohydrate restricted diet in guinea pigs
Authors: Aguilar David , Deogburn Ryan , Volek Jeff S , Fernandez Maria Luz
Published: June 2021

We evaluated in guinea pigs 1) the effects of a cholesterol challenge on adipose tissue inflammation and 2) the use of carbohydrate restricted (CRD) or high carbohydrate (CHO) diets to reduce inflammation generated by the high cholesterol. Twenty male guinea pigs (10 per group) were assigned to consume a diet with 30% fat, 45% CHO and 25% protein with low (.04%) (control) or high cholesterol (0.25%). After 6 wk guinea pigs were sacrificed and adipose tissue was collected. Cholesterol challenge increased free (p=.05) and total cholesterol (p=.003) accumulation in the adipose tissue. In addition pro‐inflammatory cytokines TNF‐alpha (p=.000), MCP‐1 (p=.027) and GM‐CSF (p=.000), were higher while the anti‐inflammatory cytokine IL‐10 was lower (p=.013) in the cholesterol challenged group compared to the control. Additionally, 20 guinea pigs (10 per group) were fed with 0.25% cholesterol for 6 weeks and then assigned to either a CRD (10% energy from carbohydrate) or a high CHO diet (54% CHO). When compared to high CHO diet, the CRD group had decreased accumulation of total cholesterol in the adipose tissue. Pro‐inflammatory cytokines MCP‐1 (p=.003), TNF‐alpha (p=.000), IL‐2 (p=.048) were also decreased in the adipose tissue of the CRD group of animals. These results indicate that cholesterol challenge induces adipose tissue inflammation and CRD is a better strategy than high CHO diet to attenuate this detrimental effects.
Sustanon Administration Induces Satellite Cell Proliferation and Giant Fiber Formation in Growing Skeletal Muscle without Exercise
Authors: Allouh Mohammed Zohair , Aldirawi Mohammed Hasan
Published: June 2021

Sustanon is one of the most commonly used anabolic androgenic drugs to increase skeletal muscle mass and strength. This drug is a blend of four esterized testosterone derivatives: testosterone propionate, testosterone phenylpropionate, testosterone isocaproate, and testosterone decanoate. Little is known about the effects of this drug on skeletal muscle at the cellular level. This study aimed to investigate the influence of Sustanon on the morphology of skeletal muscle fibers and the distribution of myogenic satellite cells (SCs) during postnatal growth. We hypothesized that Sustanon‐induced skeletal muscle hypertrophy is associated with an increase in the number of SCs. Robust immunocytochemical techniques and morphometric analyses were used to calculate the numbers of SCs and myonuclei within pectoralis muscle of the chicken. Sustanon significantly increased pectoralis mass and fiber size. All SC indices and the number of myonuclei increased significantly by Sustanon administration. This study indicates that Sustanon can induce hypertrophy and increases the numbers of SCs and myonuclei in skeletal muscle fibers without imposed exercise. Funds for this study were provided by a grant from the Deanship of Research at Jordan University of Science & Technology.

Grant Funding Source: Jordan University of Science & Technology
The dynamics of neuropeptide Y protein expression in the developing mouse heart
Authors: Sverkunova Anna , Dedkov Eduard I
Published: June 2021

The current study investigates the spatio‐temporal pattern of neuropeptide Y protein expression in coronary vessels and cardiac nerves during development of the mouse heart. The hearts of the C57BL/6 mice were collected on embryonic days 16 to 19 and on postnatal days 3 to 21. They were immersion‐fixed with 4% PFA/PBS and processed for cryo‐sectioning. The serial histological cross‐sections through the heart ventricles were immunostained with an antibody against NPY alone or in combination with Griffonia simplicifolia IB4 lectin, the antibodies against α‐smooth muscle (SM) actin and 150 kDa neurofilaments. We found that during embryonic and postnatal development, the coronary vessels demonstrated a high level of variability in the intensity of NPY immunostaining. Furthermore, whereas during embryogenesis, NPY was primarily expressed in the endothelial cells (ECs) of the coronary vessels, in postnatal period, the NPY immunostaining was typically detected in vascular SM cells. More importantly, the disappearance of NPY expression in ECs closely correlated with a significant expansion of NPY‐containing perivascular nerves. Therefore, our findings suggest that NPY has distinct dynamics of expression within the cells of developing coronary vessels and perivascular nerves, indicating its potential involvement in regulation of coronary vessel formation and/or function during development of the mouse heart.

Grant Funding Source: Internal Award from the NYCOM Office of Research
Feasibility of in vivo 3D microCT imaging of cortical bone vascular porosity in the rat
Authors: Pratt Isaac Vorster , Cooper David Michael Lane
Published: June 2021

Cortical bone is a dynamic tissue which undergoes adaptive and pathological changes through life. An improved understanding of the spatio‐temporal nature of these changes holds great promise for aiding the study of bone development, maintenance and senescence. Commercial in vivo microCT scanners operate with maximal resolutions in the 10–20 um range producing doses of 0.5–1 Gy for trabecular bone imaging. As dose scales exponentially with resolution, in vivo visualization of cortical microarchitecture remains beyond the reach of these systems. This study explored the feasibility of utilizing synchrotron propagation phase contrast microCT to resolve vascular porosity in the cortex of rat bone with doses suitable for in vivo imaging. We imaged ex vivo rat distal limbs at the Canadian Light Source synchrotron, determined the optimal propagation distance and used ion chamber and thermoluminescent dosimetry to measure dose. We found that 10 um resolution with 0.6 m of propagation distance at 37 keV was sufficient to visualize cortical pores with doses in the range of 2–4 Gy. Further optimization of the scan protocol promises to reduce dose to levels comparable to conventional trabecular bone scans.

Grant Funding Source: NSERC
Depicting Structure and Function of Complex Skeleto‐Muscular Systems in 3D: The Singing Behavior of a Songbird, Cardinalis cardinalis, as a Model for Human Speech
Authors: Blevins Caroline E. , Ge Jinghua , Suthers Roderick A , Homberger Dominique G
Published: June 2021

Functional and kinetic analyses of complex skeleto‐muscular systems with multiple semi‐independent parts have traditionally been a challenge. We have used recent developments in x‐ray CT scanning, 3D reconstruction, imaging, computation, animation, and anatomy to analyze such a system: The vocal apparatus of a songbird, the Northern Cardinal, as a model for human speech. In a 3D reconstruction and visualization through the software Avizo of an x‐ray CT scan, the shoulders, neck, skull, upper jaw apparatus, mandible, hyoid apparatus, trachea, and laryngeal apparatus were segmented (i.e., individually marked). This 3D model was imported into the software Maya to be animated by the computer animation technique called “character rigging”. To match the movements of the animated 3D model to those of a living bird, proper kinematic constraints were applied to the rig. The 3D model was then animated frame by frame by pose matching to the image sequence of an x‐ray video of a singing bird. The correct position of the skeletal elements was checked in various views to account for variations in roll, yaw, and pitch. By adding the sound‐track of the x‐ray video, we matched the exact anatomical configuration of the complex 3D model to each syllable of the song. This method requires more investment at the front end, but allows the modeling of various movements once the 3D model has been constructed. Supported by NIH grant NINDS R01 NS029467 to RAS

Grant Funding Source: NIH grant NINDS R01 NS029467
Decreased parvalbumin mRNA expression in dorsolateral prefrontal cortex in Parkinson's disease
Authors: Lanoue Amelie , Blatt Gene , Soghomonian Jean‐Jacques
Published: June 2021

Gene expression of the 67 kilodalton isoform of the GABA synthesizing enzyme, glutamic acid decarboxylase, is decreased in the dorsolateral prefrontal cortex (DLPFC) in Parkinson's disease (PD) (Lanoue et al., 2010, Experimental Neurology). Parvalbumin (PV) is a calcium‐binding protein expressed by a subset of GABAergic interneurons in the cerebral cortex. Computational models show that decreased cortical GABA and PV levels reduce gamma oscillatory activity (Volman et al., 2011, J. Neuroscience) and cortical oscillations are altered in PD. To test the hypothesis that PV levels are decreased in the cerebral cortex in PD, PV was analyzed on post‐mortem tissue from DLPFC from PD and control cases. Radioisotopic in situ hybridization histochemistry was used to examine PV mRNA expression. Quantitative image analysis of emulsion radioautographs showed a significant decrease in mRNA labeling per neuron in PD compared to control brains. Immunohistochemistry was used to label PV‐positive neurons in fixed tissue sections. Design‐based stereology indicated that the average density of PV‐labeled neurons was not significantly different between groups. In conclusion, PD is paralleled by a decrease in PV gene expression without loss of PV neurons in the DLPFC. Decreased PV expression in cortical GABAergic interneurons may be contributing to altered oscillations in PD. American Parkinson's Disease Association
Mapping the anatomical connectivity in the language‐specific cerebrocerebellar network
Authors: George Ian , Christ Shawn , Aldridge Kristina
Published: June 2021

Human language requires a network of specialized areas and connections in the brain to process this complex function. The classical neuroanatomical model of human language includes two cerebral areas (Broca's & Wernicke's) serving speech production and comprehension, respectively. Functional neuroimaging studies have demonstrated that the cerebellum is also involved with overt speech planning and production, rather than its motor execution. The functional and anatomical connections of this network however, are poorly understood. In this study we define the structural connectivity of the language‐specific cerebrocerebellar network (LSCN) between the cerebrum and cerebellum. Using a combination of high resolution structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to map the the complex morphology of LSCN in five healthy adults. The LSCN includes the right lateral cerebellum, the primary language centers in the left cerebrum, and the white matter pathways between them connecting through the thalamus. This robust network analysis of the language centers of the brain provides a powerful normative framework of comparison to uncover the basis and possible causes of neurodevelopmental and neurodegenerative disorders that affect language, as well as the anatomical framework for the evolution of language.

Grant Funding Source: MU Life Sciences Fellowship and DODC‐DMRP #AR093087
Dysregulation of brain divalent metals ions as a possible cause for lead‐induced deficits in learning and memory
Authors: Khan Khalid M , Rahman Abdur , Attur Sreeja M , Srikumar T. S.
Published: June 2021

Lead (Pb) is a known toxicant which affects the central nervous system. We have previously shown that the activity/expression of serine/threonine protein phosphatases is dysregulated by Pb exposure (Rahman et al, 2012). Since the activities of several serine/threonine phosphatases are modulated by divalent metal ions, we investigated the blood and brain levels of Cu, Mn and Zn. Wistar rat pups (n=10/group) were exposed to 0.2% Pb‐acetate via their dams’ drinking water from postnatal day (PND) 1 to 21 and directly via drinking water from weaning until PND 30. The control group (n=10) was given regular water. Pb, Cu, Mn and Zn in blood and brain tissues were measured by atomic absorption spectrophotometer. Morris water maze was used to test learning and memory. Mean values of Pb in blood and brain in Pb‐exposed rats were significantly (p < 0.05) higher than in control animals at PND21 and PND30. At PND21 blood and brain levels of Cu, Mn and Zn significantly decreased in the Pb‐exposed rats. At PND30, brain levels of both Cu and Zn were decreased in the Pb‐exposed rats, whereas, brain Mn was not affected. Pb exposure also resulted in significant impairment of learning. These data suggest that exposure to Pb during early postnatal development of brain causes dysregulation of essential divalent metal ions Cu, Mn and Zn. Since these metal ions are necessary co‐factors for many enzymes in the brain, including protein phosphatases, their substantial reduction in the brain of Pb‐exposed rats may result in altered phosphatase activity (PP2A for example) and subsequent functional impairment. One such related metabolic derangement is tau hyperphosphorylation due to decreased PP2A activity. This PP2A‐associated hyperphosphorylation of tau may be involved in Pb‐induced deficits in learning and memory as well.
Investigating neurogenesis with biosensors directed at key transcription factors
Authors: Stoddard Matthew R , Bonham Andrew J
Published: June 2021

Neurogenesis, the process by which neural stem and progenitor cells turn into functional neurons, is heavily regulated. Much of this regulation comes from the interplay of transcription factor proteins that direct the expression of key genes. Two of these transcription factors are the proteins Ascl1 and Lmo4 which regulate genes involved in neuronal commitment and the generation of autonomic neurons among other important genes in development of nervous cells. Ascl1 and Lmo4 mutants are known to be involved in human diseases including neuroblastomas and small cell lung cancers. Deletion of either gene has resulted in death when tested in mouse models. Many details of the roles Ascl1 and Lmo4 play in neurogenesis, human disease, and how they interact with one another are not fully understood. To address these outstanding questions, we are generating sensitive, DNA‐based biosensors for the quantitative detection of the DNA‐binding activity of these significant proteins. These sensors will be used with recombinantly expressed and purified constructs of human Ascl1 and Lmo4, with the goal of determining the effect of protein‐protein interaction on their regulatory activity.
A DNA damage‐inducible response in Acinetobacter baumannii
Authors: MacGuire Ashley Erin
Published: June 2021

Acinetobacter baumannii favors chromosomal insertions and rearrangements, lending to its ability to gain antibiotic resistance and succeed as a pathogen. This tendency toward genomic plasticity contradicts efforts of other organisms to preserve their genomes. In turn, it was thought that A. baumannii was missing a DNA damage‐inducible response, which would play a role in maintenance of chromosomal integrity. We sought to characterize such a response in A. baumannii, using fluorescent reporter strains to examine gene induction. We found A. baumannii not only to possess a DNA damage‐inducible system, but genes regulated under this system are induced under bistable promoters. This bistable induction of genes after DNA damage is not seen in other organisms such as Escherichia coli and could allow A. baumannii to take risks, allowing heightened recombination and mutagenesis in a portion of the population, without risking the whole cell line. The control of A. baumannii outbreaks has become a serious problem in hospitals, as multidrug resistance rises. Further insight into the workings of this bistable system will be critical in the growing search for therapies against this increasingly adaptive bacterium.
p54nrb/NONO Regulates Glucocorticoid Production by Controlling the Capacity for cAMP Signaling
Authors: Yang Jia , Sewer Marion B.
Published: June 2021

Glucocorticoid production is a finely tuned integrated process that is activated by the cAMP/protein kinases A (PKA) signaling pathways. Previous studies have demonstrated that p54nrb/NONO is a transcriptional coregulator of genes required for glucocorticoid production. Moreover, p54nrb/NONO is implicated in bridging transcription and splicing. Thus, we sought to define the molecular mechanism by which p54nrb/NONO regulates glucocorticoid biosynthesis. Silencing p54nrb/NONO expression in H295R human adrenocortical cells attenuated adrenocorticotropin‐stimulated cAMP production. In addition to a decrease in intracellular cAMP concentrations p54nrb/NONO knockdown cells exhibited reduced expressions of multiple genes required for cAMP signaling, including the catalytic subunits of PKA, members of the activating transcription factors (ATF)/cAMP response element binding (CREB) family of transcription factors, and members of the nuclear receptor 4A family. Reduced cAMP signaling capacity was concomitant with a decrease in the expressions of key enzymes required for steroid hormone production, CYP17A1 and CYP11B1. Finally, suppressing p54nrb/NONO reduced the secretion of cortisol and dehydroepiandrosterone. In summary, we identify p54nrb/NONO as a novel regulator of cAMP concentrations, and thus the cAMP signal transduction cascade.
Inhibition of polyisoprenylated methylated protein methyl esterase: a putative biomarker and therapeutic target for pancreatic cancer
Authors: Aguilar Byron J , Amissah Felix , Duverna Randolph , Poku Rosemary A , Lamango Nazarius S
Published: June 2021

Pancreatic cancer (PC) is the fourth leading cause of cancer deaths and often develops without early symptoms. The abysmal 5‐year overall survival rate of only 6% has fueled the search for novel biomarkers and drug targets. Mutations in K‐ras are involved in >;90% of PC and enzymes that target ras metabolism have been explored as anticancer drug targets. The polyisoprenylation pathway (PP) is essential for proper ras function. Inhibition of polyisoprenylated methylated protein methyl esterase (PMPMEase) induces the apoptosis of various cancer cells. Immunohistochemical analysis of a PC microarray revealed overexpression of PMPMEase compared to controls. Mean PMPMEase staining intensity for pancreatic ductal adenocarcinoma (393.6±14.4) was statistically greater than normal (115.0±7.6, p<0.0001) and normal adjacent tissues (145.0±8.6, p<0.0001). Polyisoprenylated cysteinyl amide inhibitors (PCAIs) designed as potential anticancer drugs showed micromolar Ki values against PMPMEase. Taken together, PMPMEase may serve as a novel biomarker and drug target in the management of pancreatic cancer.
Correlation between Genotypes and Behavioral Phenotypes in a Mouse Model simulating aspects of Human Post‐traumatic Stress Disorder (PTSD)
Authors: Srinivasan Seshamalini , Sowe Bintu , Miller Stacy‐Ann , Muhie Seid , Chakraborty Nabarun , Hammamieh Rasha , Meyerhoff James , Jett Marti
Published: June 2021

Biologically meaningful correlations between behavioral phenotypes and genotypes are evaluated in a modified ‘residentintruder’‐ type stress on mice. This model was established by housing male C57BL/6 naïve subject mice with an SJL aggressor (Agg) mouse without direct contact for 6 h/d for 10 d or 5 d, and then briefly pairing the C57BL/6 mice with the Agg mice for 3x/d. Controls (C), also housed without food/liquid during the 6hr session, did not experience direct physical contact with Agg. At time points of 24 hours or 6 wks after the last exposure, behaviors of C and aggressor‐exposed (Agg‐E) mice were studied using the partition test, which allows mutual exposure of only sensory cues without physical contact. Behavioral patterns (partition avoidance, freezing) of Agg‐E mice suggested fear and social withdrawal, the reported traits of PTSD. Global gene expression profiling of three major stress‐relevant brain regions, namely Hippocampus (HC), Amygdala (AY), and Medial Pre‐Frontal Cortex (mPFC) shows a clear genotype distribution between the C and Agg‐E in AY and not in HC which is a positive correlation with PTSD symptom severity. The cluster pattern of MPFC reflects similarity between the genotype profile and behavioral phenotype. Further comprehensive analysis can potentially lead to identifying diagnostic and therapeutic biomarkers that serve as internal indicators of the complex psycho‐pathogenesis.
TNFR2 induces IRF‐1 dependent IFNβ autocrine signaling in endothelial cells to promote monocyte recruitment
Authors: Venkatesh Deepak A , Ernandez Thomas , Rosetti Florencia , Batal Ibrahim , Cullere Xavier , Zhang Yuzhi , García‐Cardeña Guillermo , Stavrakis George , Horwitz Bruce , Mayadas Tanya N
Published: June 2021

Endothelial mechanisms of neutrophil recruitment are well studied but the signals that promote mononuclear cell influx remain unclear. We discovered that acute TNF stimulation of murine microvascular endothelial cells, which express TNFR1 and TNFR2 strongly induced mononuclear CXCR3 chemokines through Interferon regulatory factor‐1 (IRF‐1) induced IFNβ synthesis, and subsequent autocrine signaling via the IFNα/β‐receptor and STAT1. Both TNFR2 and TNFR1 were required for IRF‐1‐IFNβ signaling induced by soluble TNFα. A role for TNFR2 in the induction of IRF‐1, IFNβ and CXCR3 chemokines was confirmed following its overexpression and ligand independent activation in human endothelial cells. In vivo, acute renal inflammation induced by intravenously administered recombinant TNF resulted in neutrophil and monocyte recruitment in the kidney that required TNFR1, while the TNFR2‐IRF‐1‐IFNβ autocrine loop was essential only for monocyte/macrophage accumulation. In a chronic model of anti‐glomerular basement membrane nephritis, IRF‐1 and renal expressed TNFR2, but not TNFR1, were essential for sustained macrophage accumulation. Thus, our data identify a previously unrecognized signaling pathway in endothelial cells that is responsible for selectively recruiting monocytes during a TNF‐induced inflammatory response.

This work was supported by the NIH PO1HL036028, RO1 DK51643 ( T.M.)
Development of Photocrosslinkable Class I Peptide‐Major Histocompatibility Complex (pMHC) Monomers for Detecting Antigen‐Specific T Cells
Authors: Rincon Mariah Paula , Xie Jianming
Published: June 2021

A method using pMHC able to be crosslinked by UV irradiation acting on a 4‐azidosalicyclic acid (ASA) group on the peptide adjacent to the recognition sequences has been successful at labeling antigen‐specific T cells with excellent specificity and efficiency. However, studies with photocrosslinkable pMHC class I ligands are more challenging, since an ASA on the peptide interferes with T cell receptor (TCR) binding. In order to generate functional ligands to detect human TCRs, we first incorporated an ASA on the pMHC peptide through an 8‐residue extension. A second approach relied on designing a ligand where the ASA is attached to sites on the MHC molecule instead of the bound peptide, which allows for the incorporation of peptides in their native form. Seven recombinant human pMHC ligands were generated with, and then modified with ASA to produce photocrosslinkable HLA‐A*0201 molecules. Ultimately, flow cytometry will enable to determine which monomer is the most efficient at staining CMV‐specific CD8+ T cells in human peripheral blood mononuclear cells. In conclusion, we generated the precursors to a technology that allows staining of T cells specific for peptides bound to MHC class I molecules.
Lack of nuclear BMP‐2 causes reduced spleen size
Authors: Olsen Daniel S , Bailey K Tyson , Nichols Brandt A , Bridgewater Laura C
Published: June 2021

Nuclear bone morphogenetic protein 2 (nBMP2) is a nuclear variant of the secreted growth factor BMP‐2. Experiments in nBmp2NLStm mutant mice, which lack nBMP2 in the nucleus, revealed that nBMP2 affects intracellular calcium transport in skeletal muscle and hippocampal neurons. The objective of this study was to determine whether nBMP2 affects the immune system, since activation of lymphocytes and other immune cells depends on intracellular calcium transport. We found that spleens in nBmp2NLStm mutant mice were 28% smaller than in wild type mice. When mutants and wild types were challenged with an intravenous infection of 107 CFU of S. aureus, wild type mouse spleens increased in mass by an average of 63%, while mutant mouse spleens increased by 76% by the third day after infection. Liver and kidney mass were not different between mutant and wild type, either before or after infection. The white pulp of the spleen contains many immune cells, particularly B and T lymphocytes and reduced spleen size in the nBmp2NLStm mutant mice could be caused by a reduced number of lymphocytes migrating to the spleen. Samples of blood, liver, spleen, kidney and lymph nodes cultured three days after infection showed no difference in post infection bacterial load between mutant and wild type, suggesting that the innate immune response is functional in nBmp2NLStm mice.

Supported by NIH #AR048839
Dual Routes for Bacteriovorus bdellovibrio Asparaginyl‐tRNA Formation
Authors: Alperstein Ariel , Sheppard Kelly
Published: June 2021

Two distinct paths have evolved in nature to attach the amino acid asparagine (Asn) to its cognate transfer RNA (tRNAAsn), an essential step in translation. In the first (the direct pathway), Asn is directly ligated to tRNAAsn by asparaginyl‐tRNA synthetase (AsnRS). In the second (the indirect pathway), a non‐discriminating aspartyl‐tRNA synthetase (ND‐AspRS) attaches Asp to tRNAAsn, and then GatCAB transamidates the Asp to Asn on the tRNA. Bioinformatic analysis predicts the predatory bacterium Bacteriovorus bdellovibrio codes for both pathways. Our work has focused on whether B. bacteriovorus encodes a ND‐AspRS and GatCAB for tRNA‐dependent Asn biosynthesis. Our studies, using the E. coli Asn auxotrophic strain JF448, demonstrate that together the B. bacteriovorus AspRS and GatCAB can synthesize Asn on tRNA. The non‐discriminating nature of the B. bacteriovorus AspRS is being further verified by using the E. coli TrpA34 system and in vitro studies. We speculate encoding dual routes for Asn‐tRNAAsn formation enables B. bacteriovorus to grow efficiently in the presence and absence of a host.
A relation between biochemical tumor markers and dietary factors of healthy men and women
Authors: Kang Myunghwa , Park Seungmi , Oh Doo‐Nam , Kim Mi‐Hyun , Choi Mi‐Kyeong
Published: June 2021

The purpose of this study was to investigate a relation between tumor makers and dietary factors of healthy adults. We analyzed tumor related markers (CEA, AFP, PSA, CA125) in blood, daily food and nutrient intake by using a 24‐hr recall method to healthy 23 men and 32 women. The average age of subjects was 50.7 years for men and 48.9 years for women. The height and weight were significantly higher in men; meanwhile the body fat was higher in women. There were no substantial differences between the men and women in biochemical tumor markers and food intake. However, daily energy intake of the men was significantly higher than that of the women (2279.2 kcal vs. 1541.4 kcal, P<0.01). Blood CEA, a general biomarker of various cancers, had a significant and negative correlation with men's energy intake and women's food intake. There was a significant and positive correlation between blood AFP, biochemical markers of liver cancer, and serum GOR/GPT in both men and women. Blood PSA, biomarker of prostate cancer in men, is significantly and positively correlated with animal iron intake. Further studies are needed to elucidate the relationship between biochemical tumor markers and dietary factor.
Effects of dietary protein quantity on sleep quality in energy‐restricted overweight and obese adults
Authors: Zhou Jing , Armstrong Cheryl LH. , Campbell Wayne W.
Published: June 2021

Research suggests ingesting protein before sleep may improve sleep quality, but the effect of habitual protein intake on sleep quality is not well known. For this pilot study, nine overweight/obese people (6F:3M, age 59 ± 11 y, BMI 30.0 ± 1.6 kg/m2, mean ± SD) consumed lacto‐ovo vegetarian diets with an energy restriction (ER) of 750 kcal/d below need for 3 months. During this time, each person randomly completed three consecutive 4‐wk periods with the diets containing 10, 20 or 30% of total energy from protein. At baseline and the end of each ER period, global sleep quality (GSQ) was assessed using the Pittsburgh Sleep Quality Index questionnaire. GSQ scores range between 0–21 arbitrary units (au) with a higher value representing worse GSQ during the preceding month. At baseline, 78% of the participants were classified with poor GSQ (>;5 au), and 44%, 56%, and 11% had poor GSQ while consuming 10%, 20%, and 30% protein during ER, respectively. During ER, GSQ was lower when 30 vs. 10% protein was consumed (4.38 ± 1.51 vs. 5.78 ± 2.59, P = 0.05), with 20% protein intermediate (5.67 ± 2.69). When expressed as change from the previous month, delta GSQ was larger for 30% (−1.75 ± 1.49) vs. 20% (−0.11 ± 0.78) and 10% (0.13 ± 1.13) protein (P = 0.0179). These results suggest that consuming a greater proportion of energy from protein may improve global sleep quality during weight loss.

Grant Funding Source: The Beef Checkoff, National Pork Board, and NIH RR025761
Effect of race of interviewer on energy underreporting from food frequency questionnaires in a predominantly African American population
Authors: Huye Holly F. , Rupp Renee , Connell Carol
Published: June 2021

Dietary recalls are common practice in health assessments measuring nutritional status. Previous research has identified characteristics of people who are more likely to underreport, but little research has been done to determine if ethnic match between interviewer and participant influences underreporting. The purpose of this research was to assess effect of race of interviewer on underreporting in a predominantly black population. The analysis used 290 food frequency questionnaires collected at a 3‐month health assessment for a nutrition education intervention in the Lower Mississippi Delta (LMD). A predicted total energy expenditure formula by Vinken et al. was used to determine underreporting and indicated 67.5% were underreporters. The majority of the sample was black females (89.6%), aged ≥41(82.8%), had some college or higher (67.3%), had income over $20,000, and classified as obese (69.9%). 41.4% were interviewed by a white interviewer; 58% were interviewed by a black interviewer. A multiple linear regression model using a dichotomous underreporting variable as the dependent variable and race of interviewer, BMI classification, education level, and income level as independent variables was significant (p < .0001). However, race of interviewer was not a significant predictor in the model, suggesting race does not influence underreporting in this population. USDA/ARS project 58–6251‐8–043
Effect of multiple micronutrient supplementation on the neurodevelopment of HIV‐exposed Tanzanian infants
Authors: McDonald Christine , Manji Karim , Kupka Roland , Okuma James , Bosch Ronald , Kisenge Rodrick , Aboud Said , Bellinger David , Fawzi Wafaie , Duggan Christopher
Published: June 2021

Background

Micronutrient deficiencies are common in sub‐Saharan Africa and are associated with impaired infant neurodevelopment. Exposure to HIV in utero may also adversely affect neurodevelopment.

Objective

To evaluate the effect of daily multiple micronutrient supplementation on the neurodevelopment of HIV‐exposed Tanzanian infants.

Methods

Infants were randomized to receive daily oral supplementation of multiple micronutrients (vitamins B complex, C, and E) or placebo from 6 weeks of age for 24 months. The Bayley Scales of Infant Development, 3rd edition (BSID‐III) were administered a subset of 192 infants at age 15 mo. Multivariate regression models were used to compare the difference in scores between treatment groups.

Results

The prevalences of male sex, preterm birth, and low birthweight were 52.6%, 16.2%, and 5.2%, respectively. After adjusting for sex and BSID‐III administrator, there were no significant differences in raw cognitive, gross motor, expressive or receptive language scores. There was a trend toward improved fine motor skills among infants in the micronutrient group (difference in means = 0.38; 95% CI = −0.01, 0.78; p=0.06).

Conclusions

Daily multivitamins did not significantly improve the neurodevelopment of HIV‐exposed infants. Alternative strategies to improve child development should be explored in the context of HIV.
Differing effects of statistical approaches to assess the relationship between egg consumption patterns and adiposity using data from 2001–2008 NHANES
Authors: Nicklas Theresa A. , O'Neil Carol E. , Fulgoni Victor L.
Published: June 2021

Associations between food patterns and adiposity are poorly understood. Three statistical approaches examining the association between egg consumption and adiposity were tested. Participants (n=18,987) were 19+ years from 2001–2008 NHANES. 24 hour diet recall data provided intake; body mass index (BMI) and waist circumference (WC) determined adiposity. Least‐square means ± SE, adjusting for appropriate covariates, were generated. The first statistical approach categorized participants into egg or non‐egg consumers. Consumers had higher mean BMI (p=0.006) and WC (p=0.002) than non‐consumers. Second, cluster analysis identified 8 distinct egg consumption patterns (explaining 34.5% of the variance in total energy intake). Two egg patterns (egg/meat, poultry, fish [MPF]/grain/vegetables & egg/MPF/grain), consumed by ≤2% of the population, drove the association (compared with no egg pattern) between egg consumption and BMI and WC. The third approach controlled for other food groups consumed with eggs in those two egg patterns. Only the egg/MPF/grain pattern remained associated with BMI and WC (both p≤0.0063). Care needs to be taken with data interpretation of diet and health risk factors and the choice of statistical analyses since these studies are used to generate hypotheses. Additional studies are needed to better understand these relationships. Support: USDA & Egg Nutrition Board.
Academic Experts’ Perceptions Related to a Positive Mealtime Environment in Childcare Settings.
Authors: Isgrig Hunter Adams , Mita Satoko C , Goodell L Suzanne
Published: June 2021

The Academy of Nutrition and Dietetics states, “Child‐care providers should be knowledgeable about… strategies for creating a positive mealtime environment.” However, the position paper does not define or describe a positive mealtime environment. To assess how academic experts define a positive mealtime environment, researchers interviewed experts across the country specializing in child feeding practices or childhood development. Analysis of transcripts revealed a relationship between the physical and psychosocial environments in the classroom, which contribute to the development of a positive mealtime environment. The physical environment includes subjects such as the architecture of the room, child‐friendly utensils, as well as age‐appropriately prepared food. The psychosocial relationship depends on the teachers’ ability to utilize her knowledge, confidence, and resources to construct a positive mealtime environment. Our results will be used to develop educational materials for preschool teachers, showing them how to construct and understand the benefits of a positive mealtime environment.

Grant Funding Source: none
Nutrition Messages in Mainstream and Ethnic Minority Women's Magazines Over Three Decades: A Content Analysis
Authors: Landman Rissa , Yeh Ming‐Chin , Keeney Melissa , Leung May May , Navder Khursheed
Published: June 2021

Objective

Editorial content in mainstream (Glamour) and ethnic minority (Essence) women's magazines was examined to identify trends and compare nutrition and health‐related messages to dietary recommendations.

Methods

Four years in each decade (1980s, 1990s, 2000s) and three issues in each year were examined for both magazines. Editorial content focusing on food, nutrition, and physical activity was included. Messages were tallied for each theme for each decade. A percentage was calculated for each theme to compare the two magazines. Inter‐rater reliability index of 0.96 was obtained using the coefficient of agreement.

Results

Glamour was more likely to advise about caloric counting and restriction than Essence across all decades (18.1 vs.12.5%, 21.1 vs. 2.3%, 27.8% vs. 4.2%). In the first two decades, Essence was more likely to write about dietary fiber and whole grains than Glamour (18.8 vs. 11.1%, 13.9 vs. 7.9%). During the 2000s, Glamour covered the topic more often (14.8%) than Essence (4.2%). Both magazines emphasized proper nutrition messages, such as consuming adequate fiber and fruit and vegetable intake, moderating fat intake and limiting saturated fat consumption.

Conclusions

Despite slight differences in theme emphasis, the magazines appear to be an acceptable source of nutrition information that is in line with dietary recommendations. No funding to disclose.
Analysis of allostatic load and eating behaviors among healthy young women with different body types
Authors: Horiguchi Masami , Maruyama Ryoko , Tanaka Gohichi
Published: June 2021

Allostatic load refers to the cumulative effects of chronic stress on the body. The aim of this study was to analyze the allostatic load index and eating behaviors. The participants included 137 healthy women, who were divided into the lean group, the standard group, and the standard body mass index (BMI) obesity group. Their mean age was 18.7 (SD1.0). Allostatic load index, as a cumulative risk marker, was defined as the mean standard scores of the 10 variables such as systolic blood pressure and triglyceride. The mean of allostatic load index scores were follows: −0.12 in the lean group, −0.04 in the standard group, and 0.19 in the standard BMI obesity group (F(2, 132) =4.45, p<0.05). There was a significant difference in the eating behavior scores of the lean and standard BMI obesity groups (F(2, 132) =3.59, p<0.05). These findings suggest that women in the standard BMI obesity group experience more stress during their daily lives and have more unhealthy eating behaviors than women in the other 2 groups. This study was supported in part by a grant‐in‐aid for Scientific Research (C) to Masami Horiguchi from the Japan Society for the Promotion of Science (grant no.21592855).