bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term vegetarians have higher levels of antioxidant nutrient intakes and reduced level of oxidative stress marker compared to omnivores
Authors: Kim Mi Kyung , Jo Jung Hee , Kim So Hyeon , Park Yoo Kyoung
Published: June 2021

A vegetarian diet has been generally known to be conducive to good health. Oxidative stress can cause chronic disease as a result of cell injury, one of the many ways to reduce oxidative stress is through consuming vegetarian diet containing affluent antioxidant vitamins. The purpose of this study was to compare antioxidant status, oxidative stress and blood lipid profiles between long‐term vegetarian and age‐ and sex‐ matched omnivores. A total of 45 vegetarians (male n=23, female n=22; 49.5±5.3 years) who had been vegetarians for ≥10 years and 30 omnivores (male n=15, female n=15; 48.9±3.6 years) participated in this study. The levels of derivatives of reactive oxygen metabolites (d‐ROMs) and lipid profiles were analyzed. Diet was assessed through 24‐hr recall for 3 consecutive days (2 weekdays and 1 weekend day). Intakes of vitamin A (p<0.005), vitamin C (p<0.005) and β‐carotene (p<0.001), but not vitamin E, were significantly higher in the vegetarians. The level of d‐ROMs was 10% lower in the vegetarians suggesting lower oxidative stress (p<0.05). The levels of total and LDL‐cholesterol in the vegetarians were significantly lower than that in the omnivores (p<0.05). These results suggest that long‐term vegetarian diet would provide health benefits, partially explained oxidative stress reduction.
McHealthy: How Frequent Dining Program at Fast Food Restaurant Increases Healthy Eating Intention
Authors: Chan Elisa Ka Yan , Wansink Brian
Published: June 2021

In an effort to instill loyalty, fast food restaurant often establishes reward programs. Such programs may take the form of sweepstakes (e.g. McDonald's Monopoly), giveaways (i.e. Free Coffee Fridays at Burger King), and reward points for redemption (e.g. Subway Card). Although often criticized for contributing to unhealthy eating, fast food restaurant may actually create a win‐win situation by extending the time horizon of purchase consideration of its loyalty reward program. This research answers the question: how frequent dining program at fast food restaurant increases healthy eating intention. In a study of fifty subjects, people are asked how likely they will switch from French fries to salad at a fast food restaurant. The incentive for switching is either a price discount or points reward. Results show that those who self‐reported to care mostly about taste (i.e. hedonist) are more likely to make the healthy switch when offered points reward than a price discount (p=.023). More importantly, patrons of the fast food restaurant also display higher intention to switch in the points reward condition (p=.039). These findings show that fast food restaurant can simultaneously enhance the health and loyalty of its customers. They are also useful for campus cafeteria and school meal providers to promote healthy eating.
Nutritional impact of adding one serving of dairy foods to the U.S. diet
Authors: Fulgoni Victor , Keast Debra R. , Quann Erin E. , Auestad Nancy
Published: June 2021

The 2005 Dietary Guidelines recommends three cup equivalents (CEQ) of low‐fat or fat‐free milk or milk products (MMP) for those 9+ yrs. Current intake of MMP is 1.8 CEQ/day (2+ yrs). Changes in energy and nutrient intakes were modeled if 25, 50 or 100% of the population increased MMP just one CEQ/day using NHANES, 2003–2006, data for subjects 2+ yrs (n=16,882) with reliable 24‐hr recall records on Day 1. A consumption weighted composite of currently consumed MMP was used. If 100% of the population increased MMP one CEQ/day, increases in average intakes/day would be 143 kcal, 9.2 g protein, 6.8 g total fat, 4.2 g saturated fat; 116 μg retinol activity equivalents, 0.4 mg, 1.0 μg and 2.2 μg for vitamins A, B2, B12, D, respectively; and 301, 244, 24, 1.2, 212 and 297 mg for calcium (Ca), phosphorus (P), magnesium, zinc, sodium (Na) and potassium, respectively (p<0.05). If 25% the population increased MMP one CEQ/day vitamin D, Ca and P would increase significantly, while if 50% the population increased MMP one CEQ/day all variables, except Na would increase significantly (p<0.05). If low‐fat/fat‐free options were selected as recommended, rather than MMP as currently consumed, energy would only increase 81 kcal and saturated fat 0.9 g. These data show increasing MMP one CEQ/day, approximating recommendations, significantly increases intake of key nutrients in the U.S. diet and that lower fat forms are preferred to typical choices. (Supported by the National Dairy Council/Dairy Research Institute)
Anonymized, genotype‐directed online nutrition guidance
Authors: Kohlmeier Martin
Published: June 2021

Unaided tailoring of individual food selections to multiple genotype‐directed nutrient intake targets greatly exceeds the abilities of lay consumers and dietetic professionals alike. Previous draft versions provided proof‐of‐concept for computer‐assisted menu planning (http://www.nim.unc.edu/nutrition/guidance.html). Added functionalities and an expanded food database have now improved usability and consumer choice.

The personal target sets depend on user characteristics and genetic data. The user never enters personally identifying information, DNA samples are identified by code.

The algorithmic core calculates and ranks the sum of normalized parabolic distance functions relative to personal target sets of individually selectable nutrients and food groups in a potential menu. The program offers an initial choice of well‐matched daily meal plans. The user can then make unlimited modifications by replacing, adding or deleting items. Real‐time displays of color‐coded lists, which show alternative foods ranked by goodness‐of‐fit, make finding acceptable choices easy.

Initial user tests indicate that this online tool effectively supports personalized meal planning based on complex genotype patterns.
Antidiabetic effects of onion peel extracts in insulin‐resistance rat induced with streptozotocin and high fat diet
Authors: Lim YeNi , Jung Ji Young , Kim Yeon Kyoung , Moon Min‐Sun , Kim Ji Yeon , Kwon Oran
Published: June 2021

This study was performed to examine the antihyperglycemic effect of ethanolic onion peel extract, which contains high concentration of quercetin in streptozotocin‐induced diabetic rats. In the previous study, we confirmed that onion peel extract ameliorated IAUC for oral glucose tolereance test. In this study, we further analyzed the insulin sensitizing effect of onion peel supplementation. The glycogen concentration in the liver was significantly increased in the both of pure quercetin and 1.0% ethanolic onion peel extract groups (p<0.05). Insulin concentration in plasma and HOMA‐IR were not changed significantly, the plasma C‐peptide and free fatty acid (FFA) concentrations, however, were reduced by ethanolic onion peel extract in dose‐dependent manner. In addition, we revealed that the onion peel extract improved insulin resistance through antioxidant and anti‐inflammatory capacities of quercetin and other flavonoids in onion peel extracts.
Smaller concentration‐supplementation slopes at a higher vitamin D treatment dose
Authors: Barker Tyler , Dixon Brian M. , Weaver Lindell K.
Published: June 2021

There are conflicting reports regarding serum 25‐hydroxyvitamin D [25(OH)D total] concentration slope increases at different vitamin D3 supplementation doses. The purpose of this study was to normalize serum 25(OH)D concentration increases to different vitamin D3 supplementation doses. A prospective, double‐blind, placebo controlled study was conducted in healthy adults (23–43 years). Twenty‐two subjects were randomized to one of three groups: vitamin D3 supplementation at (1) 200 IU (n = 7) or (2) 4000 IU (n = 7), or (3) a matching placebo (n = 8). Supplements were taken daily for 28 days during the winter season (latitude ≈40° N). Serum 25(OH)D concentrations were measured in fasting blood draw samples obtained prior to and 7‐, 14‐, 21‐ and 28‐d after supplementation. Serum 25(OH)D concentrations increased 21‐d (P < 0.001) after 200 IU and 7‐d (P < 0.001) after 4000 IU of vitamin D3 supplementation. Following supplementation, serum 25(OH)D concentrations were greater in the 4000 IU compared to the 200 IU (P < 0.05) and placebo (P < 0.05) groups. The concentration‐supplementation dose slopes (ng/ml/100 IU) were greater (P < 0.05) following 200 IU compared to 4000 IU of vitamin D3. In conclusion, serum 25(OH)D concentration increases were greater but concentration‐dose slopes were lower at a higher vitamin D3 supplementation dose.

Sources of support: Deseret Foundation, UT and USANA Health Sciences, Inc., UT
Decorin gene expression in normal and tumor liver tissue
Authors: PARANJPE SHIRISH , BOWEN WILLIAM C , MICHALOPOULOS GEORGE K
Published: June 2021

Decorin, a small leucine ‐ rich proteoglycan is involved in a number of cellular processes. Decorin has been shown to suppress proliferation of cancer cells in vitro. Decorin interacts with a number of receptor tyrosine kinases like Met, and Epidermal Growth Factor Receptor. In view of the role of Decorin as a negative regulator of Met and EGFR, we decided to investigate whether Decorin played a role in hepatocyte proliferation, both in vitro and in vivo. Initially we investigated the effects of Decorin on induction of DNA synthesis by HGF and EGF in primary cultures of rat hepatocytes. Addition of Decorin in the culture medium resulted in more than 50% inhibition of DNA synthesis. Decorin gene expression was also found to be regulated during the early stages of liver regeneration in rats following a PHx. Decorin gene expression was found to be suppressed in Liver tissue samples obtained from HCC, Adjacent tissue, Normal and hepatoma cases by microarray analysis. We also investigated Decorin expression by RT‐PCR and western blot analysis in a number of transformed cell lines like HepG3, Hep3b and HuH7, JM1 and JM2. Decorin expression could not be detected by RT‐PCR and western blot analysis in these cell lines. In conclusion, preliminary data indicated that Decorin expression, following a PHx, is significantly suppressed during early phases of liver regeneration and Decorin has a modulating role in hepatocyte proliferation.
Identification of host cell factors involved in nuclear egress of HSV‐1
Authors: Olarte María Jesús , Schlieker Christian
Published: June 2021

All known members of the herpesvirus family assemble their capsids in the nucleus prior to envelopment in the cytosol. Capsid transport across the nuclear envelope is therefore an essential step in their life cycle. The viral gene products required for this process have been delineated, but little is known about host cell factors involved in this unusual transport route, which is distinct from the classical nuclear transport pathway. In a proteomics experiment aimed at the identification of host cell proteins involved in nuclear egress, we identified Sun2/Unc84B, a constituent of the multimeric LINC complex (linker of the nucleoskeleton and cytoskeleton) that traverses the nuclear envelope. We demonstrate co‐localization of UL34 and Sun2 to vesicular structures in the perinuclear region, and the relocalization of Sun2 in response to herpes simplex virus‐1 (HSV‐1) infection. These observations lead us to propose that HSV‐1 hijacks Sun2 to drive capsid transport across the nuclear envelope via associated cytoskeletal motors. Funding: Charles Hood Foundation, Ellison Medical Foundation.
Role of MLCL AT‐1 in Cardiolipin Metabolism: A potential Therapeutic approach to Barth Syndrome
Authors: Mitchell Ryan W. , Gale Elikana , Taylor Bill A , Hatch Grant M
Published: June 2021

Barth Syndrome (BTHS) is a rare X‐linked genetic disorder caused by a mutation in the Tafazzin gene (taz), an enzyme involved in the remodelling pathway of cardiolipin (CL). Mutation in taz results in a biochemical deficiency of CL and accumulation of monolysocardiolipin (MLCL). We investigated the contribution of another enzyme, monolysocardiolipin acyltransferase‐1 (MLCL AT‐1), to the remodelling pathway of CL in human lymphoblasts. MLCL AT‐1 or taz or both were knocked down using RNAi in normal or BTHS lymphoblasts and MLCL AT‐1 enzyme activity examined. MLCL AT‐1 enzyme activity was reduced approximately 50% (p<0.05) when MLCL AT‐1 was knocked down in normal human lymphoblasts and unaltered when taz was knocked down. Knock down of both MLCL AT‐1 and taz simultaneously did not result in a further reduction in MLCL AT‐1 activity compared to knock down of MLCL AT‐1 alone. Expression of MLCL AT‐1 in BTHS lymphoblasts with different mutations in taz elevated CL synthesis and mass over 2‐fold (p<0.05) in these cells compared to controls. These studies indicate that MLCL AT‐1 may act independently of taz. This work was supported by grants from the Manitoba Health Research Council and the Barth Syndrome Foundation (USA & Canada).
Characterization of cyclocreatine‐membrane interactions by electron paramagnetic resonance spectroscopy
Authors: Smith Virginia F. , Stampfler Jeremiah B. , Dillner Debra K. , Elgebaly Salwa A.
Published: June 2021

Cyclocreatine, a synthetic analog of the naturally‐occurring energy molecule creatine, is known to have medically‐important roles in cardioprotection and the prevention of neurodegeneration when administered alone or in conjunction with other agents. In each case, it is necessary for the cyclocreatine (CCr) molecule to cross a lipid bilayer to reach cell compartments where endogenous enzymes convert CCr to its active form, phosphocyclocreatine (PCCr). We have developed an in vitro system to study the interactions of CCr and PCCr with phospholipid headgroups and acyl chains using electron paramagnetic resonance (EPR) spectroscopy to monitor changes in the mobility of nitroxide‐labelled phospholipids in liposmes formed from bovine heart and brain lipid extracts. Cyclocreatine can be easily synthesized, using literature procedures, from chloroacetic acid and ethylene diamine. Phosphorylation of CCr with POCl3 yields PCCr. Moving the spin label to various positions along the acyl chain and headgroup made it possible to compare the effects of the two compounds at various depths of the membrane bilayer and to obtain important information about lipid mobility and dynamics. Preliminary results suggest that the presence of CCR reduces mobility of the lipid head group in a concentration‐dependent manner and that heart and brain liposomes have different responses to CCr and PCCr.
Receptor‐dependent compartmentalization of PPIP5K1
Authors: Zaremba Angelika , Shears Stephen
Published: June 2021

Inositol pyrophosphates (InsP7, InsP8) have been reported to modulate cell signaling pathways at the plasma membrane that control insulin secretion from pancreatic beta cells [1] and insulin action at target tissues [2]. We now demonstrate that the plasma membrane is also a site for receptor‐dependent compartmentalization of inositol pyrophosphate metabolism. We have studied PPIP5K1, a kinase that converts (a) InsP6 to 1/3‐InsP7 and (b) 5‐InsP7 to InsP8. Our kinetic data indicate that phosphorylation of 5‐InsP7 is the preferred reaction. We have studied the cellular distribution of FLAG‐tagged PPIP5K1 in NIH3T3 cells by confocal immunofluorescence microscopy. We recorded the concentration of enzyme at the plasma membrane relative to the cytoplasm (PM/C). This ratio was 1.7 ± 0.09 in control cells, rising to 2.9 ± 0.27 (P < 0.01) after 5 min stimulation with 50 ng/ml PDGF. Pre‐treatment with wortmannin largely prevented this effect of PDGF (PM/C = 2.1 ± 0.14), indicating a role for the PtdIns 3‐kinase pathway in directing PPIP5K1 translocation. Indeed, these results are consistent with our discovery of a novel PtdIns(3,4,5)P3‐binding domain in PPIP5K1 [3]. Following the translocation of PPIP5K1 to the plasma membrane, the enzyme's capacity to bind PtdIns(3,4,5)P3 and the expected localized synthesis of InsP8 could both influence cell‐signaling at the plasma membrane.
Cholesterol Depletion Sensitivity in a Slow Channel Congenital Myasthenic Syndrome Mouse Model: Cav‐1's Role on the Neuromuscular Junction
Authors: Grajales Jose Gabriel , Grajales Gary , Zhu Haipeng , Baez Carlos , Delgado Manuel , Nogueras Carlos , Quesada Orestes , Gomez Christopher , Lasalde Jose
Published: June 2021

Cholesterol is known to modulate membrane's biophysical properties plus influence in the function and trafficking of membrane proteins. We have shown that point mutations in the nicotinic acetylcholine receptor (nAChR) can evoke increased macroscopic responses upon cholesterol depletion and at the same time, some can result in a Slow Channel Congenital Myasthenic Syndrome (SCCMS) characterized by muscle weakness and fatigue. Our main goal is to characterize a cholesterol reduction treatment in a model in which both the SCCMS and the cholesterol sensitivity phenotype coexist, αC418W mutation. Using various approaches, we uncovered a fraction of αC418W located in caveolin‐1 rich domains, suggesting a non‐functional state and possibly susceptible to cholesterol levels. Cholesterol depletion by Lipitor® resulted in the rearrangement of these receptors to a now functional pool. After treatment, the model presented calcium overload, high caspase activity, lower motor activity and significant differentiation in relation to the neuromuscular junction and its volume under confocal microscopy. Better molecular understanding of the statins' role on membrane proteins and cholesterol's participation is crucial for novel approaches to old physiological phenomena's that haven't been solved. Ultimately addressing the biggest problem, are statins safe?
FAM129B/MINERVA is implicated in breast cancer cell invasion
Authors: Chen Song , Evans Hedeel Guy , Evans David R
Published: June 2021

FAM129B/MINERVA was previously found (Old et al (2009) Mol. Cell 34: 115) to promote melanoma cell invasion. The suppression of apoptosis plays a crucial role in cancer cell invasion and progression. Silencing the expression of the FAM129B gene did not induce apoptosis or alter the growth rate of Hela cells. However, FAM129B knockdown accelerated the response to apoptotic signals such as TNFα 3–4 fold, suggesting that suppression of apoptosis may be a mechanism by which FAM129B promotes cell invasion. FAM129B was present at very low levels in MCF10A derived from normal breast tissue and only slightly higher levels in MCF7, a malignant, but non‐invasive cell line. In contrast, very high levels of the protein were expressed in the metastatic breast cancer cell line, MDA231. Thus, FAM129B expression strongly correlates with the invasiveness of the cell and with the expression of vimentin and P120. Immunofluorescence microscopy revealed that FAM129B was present in the cell membrane, especially at cell‐cell contacts, and that the membrane localization was significantly enhanced by exposure to the PKC activator, PMA. An in vitro invasion assay showed that depletion of FAM129B from MD231 cells, significantly decreased the rate of migration through a collagen matrix as previously observed with human melanoma cells. These studies provide evidence that FAM129B may play a pivotal role in metastasis in breast cancer cells.
DNA‐dependent Protein Kinase Regulates Vascular Cell Adhesion Molecule 1 Expression in Human Vascular Cells
Authors: Ju Jihang , Naura Amarjit S. , Kim Hogyoung , Errami Youssef , Boulares Hamid
Published: June 2021

Human cell universally express high level of DNA‐PK that is not fully understood. It suggests DNA‐PK may play a secondary role in human cells.

Objective

To investigate the relationship between DNA‐dependent protein kinase (DNA‐PK) and vascular cell adhesion molecule1 (VCAM‐1) in human vascular cells.

Methods

shRNA technique and kinase inhibitor were utilized to reduce DNA‐PK activity in cultured cells; VCAM‐1 expression was analyzed using immunoblot analysis and Real‐Time PCR.

Results

Treatment with TNF induced a robust VCAM‐1 expression in the DNA‐PK‐proficient M059K cells, while such an induction was severely impaired in the DNA‐PK‐deficient M059J cells. Knocking down DNA‐PKcs expression in human umbilical vein endothelial cells (HUVEC) reduced VCAM‐1 expression after TNF treatment. The effect was confirmed by using specific DNA‐PK inhibitor, NU7026. TNF‐induced, NF‐kappa B‐dependent signal transduction was not affected by DNA‐PK.

Conclusion

DNA‐PK influences the expression of VCAM‐1 in human vascular cells. It may ultimately provide a possible therapeutic target for suppression or prevention of atherosclerosis and other related vascular diseases.
PDZK1 expression is age‐phasic in human breast cancer and a growth‐promoting factor that is indirectly regulated by estrogen through IGF‐1R
Authors: Kim Hogyoung , Ju Jihang , Naura Amarjit S , Elmageed Zakaria Y Abd , Rezk Bashir M , Abdel‐Mageed Asim B , Catling Andrew , Kim Jong‐Gug , Boulares Hamid
Published: June 2021

Although stimulation of the estrogen receptor (ER) culminates in PDZK1 expression, the mechanism by which this induction occurs and its effects in breast cancer cells remain unknown. Here we show that PDZK1 protein expression is highly associated with human breast malignancy in an age‐phasic manner in 40‐ to 62‐year‐old women displaying the highest levels of expression. 17β‐estradiol (E2) induced PDZK1 expression more than 24 h after treatment in the breast cancer cell line MCF‐7 and appeared to require an intermediate ER‐regulated gene product. Interestingly, IGF‐1R expression and function were critical for PDZK1 expression in E2‐stimulated MCF‐7 cells. PDZK1 knockdown completely blocked E2‐dependent growth of MCF‐7 cells and reduced c‐Myc expression, suggesting an involvement of the protein in cell proliferation. Ectopic expression of PDZK1 stimulated proliferation of MCF‐7 cells and enhanced the E2 growth‐promoting trait potentially through an increase in c‐Myc expression, suggesting an oncogenic function for PDZK1. Such a function may be related to the physical interaction of PDZK1 with the Src/ER/EGFR complex, but not with IGF‐1R, and enhancement of EGFR‐mediated signal transduction. These results present a novel relationship between ER and PDZK1, explain the mechanism by which PDZK1 is expressed, and suggest a novel function for the protein in the growth of breast cancer cells.
Deregulation of the transcriptional repressor ICER by phosphorylation, monoubiquitination and nuclear‐cytosolic translocation in human prostate cancer
Authors: Crow Marni , Memin Elisabeth , Genzale Megan , Molina Carlos
Published: June 2021

The transcriptional repressor ICER demonstrates a tumor suppressor function. The intended physiological role of ICER requires its presence in the nucleus of prostatic cells; however, in malignant prostate cells, ICER is undetected in the nuclei. Because the mechanisms of this phenomenon have remained largely unknown, the intention of this study was to discover the cause of ICER under‐expression in the nucleus of prostate cancer cells. These data suggest that ICER undergoes a post‐translational modification termed monoubiquitination, which enables the protein to relocate to the cytosol. This translocation is dependent upon Cdk1/cyclin B phosphorylation of ICER on serines 35 and 41. A prerequisite of ICER monoubiquitination appears to be serine 35 phosphorylation which results in a reduction in the amount of ICER in the nucleus. Rediscovery of the absent nuclear protein was isolated from the cytosolic fraction. The implications of these data are valuable for cancers that present with constitutive Cdk1 activity. This research was supported by the Sokol Student/Faculty research award.
Dyrk1A is a regulator of dendrite morphology that phosphorylates doublecortin, a microtubule‐bunding protein
Authors: Slepak Tatiana I , Lemmon Vance P , Bixby John L
Published: June 2021

To understand the phosphorylation events underlying axon/dendrite growth, we screened a cDNA library of kinases and phosphatases by overexpression in primary hippocampal neurons. One of the hits was the dual specificity tyrosine (Y) phosphorylation‐regulated kinase, Dyrk4. Overexpression of Dyrk4 increased both the number of primary neurites and the number of dendritic branches. A close relative of Dyrk4, Dyrk1A, increased dendritic branching and greatly affected the morphology of dendritic growth cones. Moreover, overexpression of several members of the Dyrk family (Dyrk1A, Dyrk2 and Dyrk3) perturbed distribution of doublecortin (DCX), a microtubule‐binding protein enriched in axonal and dendritic growth cones. Since DCX function is regulated by phosphorylation we therefore investigated the possibility that it can be a target of DYRK kinases. Co‐expression of DCX with Dyrk1A, Dyrk2 or Dyrk3, but not Dyrk4, in HEK293 cells produced lower mobility bands recognized by anti‐phospho‐DCX antibody. Sequence analysis of the DCX coding region revealed a putative phosphorylation site for DYRK kinases at serine 306 (S306). It's mutation to alanine eliminated shifted phospho bands, suggesting that S306 is indeed a target of these kinases. A more comprehensive mutational analysis suggests that phosphorylation of S306 by Dyrk kinases may prime phosphorylation by Cdk5.
An SPR‐based fragment mapping study on interleukin 2 (IL‐2) towards the development of small molecule inhibitors of protein‐protein interactions (PPIs)
Authors: Holte Kimberly , Brenke Ryan , Ochiana Stefan , Karver Caitlin , Kozakov Dima , Vajda Sandor , Allen Karen , Pollastri Michael , Whitty Adrian
Published: June 2021

To better understand how to inhibit PPI targets with small molecules, we have developed a fragment‐based method for probing the IL‐2/IL‐2 receptor alpha (IL‐2Rα) interface using surface plasmon resonance (SPR) spectroscopy. Previous SPR fragment‐binding studies used IL‐2 randomly coupled to the sensor surface. In our hands random coupling resulted in partial loss of IL‐2 activity, as measured by its ability to bind IL2Rα. We therefore prepared an IL‐2 mutant containing Ser‐Gly‐Cys at the C‐terminus to enable uniform capture of functional IL‐2 through thiol chemistry. The identity of the purified Cys‐IL‐2 was confirmed by MALDI‐TOF MS, and the absence of covalent or noncovalent aggregates was shown by gel filtration chromatography. Proper folding and functional activity were established by showing that the Cys‐IL‐2 was able to bind soluble IL‐2Rα comparably to wild‐type IL‐2, as measured by Biacore and by ELISA. The Cys‐IL‐2 is being used to measure binding of fragments derived from the 60 nM IL‐2 inhibitor reported by Sunesis Pharmaceuticals, to map how binding energy is generated by interaction with each portion of the compound in this PPI inhibitor complex. This research was supported by GM064700‐07S1 from NIGMS.
Primase: a SMART team adventure through DNA replication
Authors: Havlena Zoë , Smith‐Oistad Ivy , Petty‐Valenzuela Stephen , Bhattacharyya Basudeb , Nelson David L. , Keck James L.
Published: June 2021

DNA replication is a complex molecular process that requires the coordination of almost a dozen different proteins. Central to this molecular dance is DNA polymerase, which synthesizes new DNA strands in the 5′ to 3′ direction. While DNA is replicated continuously on the leading strand, the anti‐parallel nature of DNA coupled with the unidirectional nature of DNA polymerases poses an inherent obstacle in synthesis of the lagging strand. To overcome this challenge, organisms synthesize the lagging strand discontinuously as Okazaki fragments. Initiation of each Okazaki fragment requires an enzyme called primase, which is an RNA polymerase that synthesizes short RNA primers that can be extended by DNA polymerase.. The Madison West High School Students Modeling a Research Topic (SMART) team has modeled the core catalytic domain of DNA primase from Escherichia coli using Jmol and rapid prototyping in order to gain a better understanding of the mechanisms of DNA replication. Supported by grants from theHoward Hughes Medical Institute and NIH‐NCRR‐SEPA
Structural modeling of the Influenza virus Hemagglutinin protein in complex with a broadly neutralizing antibody
Authors: Ramirez Robert , Johnson Brendon , Nguyen Tina , Kwan James , Chowdhury Parag , Bhabha Gira , Ekiert Damian
Published: June 2021

The 1918 Spanish Influenza (H1N1) is considered one of the most disastrous pandemics in human history. It is estimated to have killed over 50 million people worldwide. The recent outbreak of H1N1 has renewed interest in this virus and the envelope proteins that allow it to enter mammalian cells. Hemagglutinin (HA) is a trimeric protein found on the surface of the influenza virus, and mediates viral attachment and entry into host cells. This protein has been the subject of intense research, as it may serve as an ideal target for the attachment of antibodies, that could prevent pathogenesis. Broadly neutralizing antibodies have the ability to bind and inhibit several subtypes of Hemagglutinin, and therefore hold much promise for therapies against influenza. CR8020 is one such broadly neutralising antibody. In a current study we look at how this antibody interacts with the stem region of the HA trimer. CR8020 binds in the stem region of HA and prevents viral fusion with the endocytic vesicle thus inhibiting the release of viral RNA into the cell. This work is important for the development of a “durable universal cross‐protective vaccine.” Supported by a grant from the HHMI Pre‐College Program.
Comparative effectiveness of two popular weight loss programs in women II: metabolic markers
Authors: Lockard B , Mardock M , Byrd M , Simbo S , Jagim A , Kresta JY , Baetge C , Jung Y , Koozehchian M , Khanna D , Oliver JM , Kyul H , Greenwood M , Rasmussen C , Kreider R
Published: June 2021

42 sedentary women (33±7 yrs, 164±7 cm; 93±19 kg; 46±7% body fat, 35±6 kg/m2) were randomized to participate in the Curves (C) or Weight Watchers (W) programs for 16‐wks. Participants in the C program followed a 1,200 kcal/d diet for 1‐wk and 1,500 kcal/d diet for 3 wks (30:45). Subjects then ingested 2,000 kcals/d for 2‐wks (45:30 CHO:PRO) and repeated this diet while participating in the Curves with Zumba program 3‐d‐wk. Remaining subjects followed the W point‐based diet program. Fasting blood samples were obtained at 0, 4, 10, & 16 wks and analyzed by MANOVA. Both programs promoted significant decreases (p<0.05) in total CHL (−5.9±11%) and LDL‐c (−8.8±17%). Significant interactions were seen in changes in total CHL (C −4.0±12, −1.9±9, −2.2±11; W −5.9±8, −7.1±10, −9.0±11%, p=0.03), LDL‐c (C −4.0±18, 1.8±15, −3.2±19; W −5.8±12, −6.8±15, −13.4±15%, p=0.03), HDL‐c (C −3.5±12, 0.1±10, 1.6±16; W −9.3±11, −9.9±12, −0.1±13%, qp=0.002), the ratio of CHL:HDL (C 1.7±11, −0.4±9, −1.9±12; W 5.1±13, 4.2±13, −7.9±10 %, qp=0.009), TG (C −6.3±27, −10.3±13, −5.4±22; W 4.1±25, −3.4±31, −0.2±43%, cp=0.03), and blood glucose (C 2.1±15, 0.7±13, −2.6±12; W −2.2±7, −3.2±10, −2.1±8%, qp=0.05). Results suggest that adherence to the W program may promote more favorable changes in blood lipids than cycling caloric intake. However, participating in the C structured diet and exercise program had more beneficial effects on HDL‐c and TG levels.
Role of apoptosis in prevention of valproic acid‐induced neural tube defects by maternal immune stimulation in CD‐1 mouse embryos
Authors: Mallela Murali krishna , Hrubec Terry
Published: June 2021

Dysregulation of apoptosis during development is a possible mechanism for teratogen‐induced birth defects. Neural tube defects (NTDs) are the second most common birth defects. Non‐specific maternal immune stimulation prevents birth defects. This study investigated the role of altered apoptosis in formation of valproic acid (VA)‐induced NTDs. Interferon‐ γ (IFN γ) was used to stimulate maternal immunity to evaluate the role of altered apoptosis in this protective mechanism. Apoptotic percentages were quantified by flow cytometry and apoptotic regions were identified by Terminal Transferase dUTP Nick End Labeling (TUNEL) assay in gestation day 9 mouse embryonic heads exposed to VA with or without maternal immune stimulation. Increased apoptosis, suggesting involvement in VA teratogenicity, was observed along the neural tube in both normal and abnormal embryos from VA‐exposed dams. Increased apoptosis in normal VA‐exposed embryos suggests that VA may alter other cellular processes such as cell proliferation and differentiation in addition to apoptosis. Apoptotic percentages in embryos with NTDs from IFNγ+VA dams were similar to controls, which indicated resistance to teratogen‐induced apoptosis. In IFNγ+VA‐exposed embryos with NTDs, immune stimulation failed to prevent apoptosis. This suggests immune stimulation protects embryos from teratogenicity of VA by preventing VA‐induced apoptosis.
Detection of rotavirus specific immunoglobulins in the serum of neonatal piglets with or without colostrum feeding
Authors: Lu Jin , Shunk Jill M. , Comstock Sarah S. , Monaco Marcia H. , Donovan Sharon M.
Published: June 2021

Rotavirus (RV) infection remains a major source of morbidity and mortality worldwide. Although RV vaccines are available, they do not confer complete protection in malnourished populations. Our long‐term goal is to develop a piglet RV vaccination model. Piglets do not receive Ig prenatally; however, porcine colostrum contains RV‐specific immunoglobulins (Ig) that are taken up by the gut. Herein, the time course of serum RV‐specific immunoglobulins was measured in piglets that were colostrum‐deprived and orally‐gavaged with sow serum for 24h (CD, n=4) or received 48h colostrum and were randomized to be sow‐reared (SR, n=6) or formula‐fed (FC, n=6). Serum RV specific IgG, IgA and IgM concentrations were measured by ELISA on d7, 14, 21 and 28. On d7, CD piglets had lower (P< 0.05) IgG than SR or FC and no detectable IgA and IgM. Overall, IgG, IgA and IgM concentrations decreased (P< 0.05) between d7 to d28 in FC and SR. IgG concentrations were greater (P<0.05) in FC than SR on d7 and d14. IgA and IgM concentrations did not differ between FC and SR between d7 to d28. Limiting colostrum intake to 48h did not reduce the serum RV specific antibodies of FC vs. SR piglets. Thus, providing serum may confer immune protection while limiting exposure to RV‐specific Ig.
B‐hydroxy‐ B‐methylbutyrate (HMB)Supplementation and Resistance Training (RT) May Improve Body Composition and Muscle Function in Healthy Elderly Men (66–78 years): A 24‐Week Study
Authors: Kendall Kristina Leigh , Stout Jeffrey R , Smith Abbie E , Fukuda David H , Moon Jordan R , Rea Marshal L , Cramer Joel T , Johnson Catherine D
Published: June 2021

To determine the effects of HMB and RT on body composition in elderly men.

METHODS

Ninty‐seven subjects (49 women, 48 men) consumed either a placebo (200 mg Calcium) or treatment (1.2g HMB‐200 mg Calcium) twice daily and enrolled into a no‐training placebo group (NT); treatment (NT‐HMB), RT, or treatment plus RT (RT‐HMB), 3.wk−1 for 12‐ and 24‐weeks. Leg extension (LE), grip strength (GRIP), get‐up‐and‐go (GUG) and dual‐energy X‐ray absorptiometry (DXA) were used to evaluate functionality, muscle mass (MM) and abdominal fat (AFM). Total Body Fat‐mass (FM) was assessed using a 4‐compartment model.

RESULTS

FM showed a significantly greater decrease for RT‐HMB compared to NT (p=0.006), NT‐HMB (p=0.001). Furthermore, changes in AFM were greater compared to NT (p=0.02), NT‐HMB (p=0.03), and RT (p=0.03). MM improved at 12‐weeks for NT‐HMB (p=0.014) and RT (p=0.004) and at 24 weeks for RT (p=0.003) and RT‐HMB (p=0.032). Week 12 muscle function increased (p≤0.01) for the NT‐HMB (LE180), RT (LE60), RT‐HMB (LE60) and at 24 weeks for NT‐HMB (LE180, GUG), RT (LE60, LE180, GRIP), and RT‐HMB (GRIP, GUG) (p≤0.01).

CONCLUSION

RT improved body composition and strength in elderly men. In addition, HMB without exercise may improve muscle mass and function in this group of subjects. Combining HMB with RT appears to augment fat loss during the first 12 weeks with no further effect at 24 weeks. Supported by Abbott Nutrition Grant.
AHCC Increases the Percent of Natural Killer Cells Post Influenza Vaccination
Authors: Sutherland Brooke Elizabeth , McCaskey Sarah , Duriancik David M , Hortos Kari , Gardner Elizabeth M
Published: June 2021

A decrease in immunity in aged populations causes an increase in influenza morbidity and mortality as well as decreased vaccine efficacy. Nutritional modulation has potential to increase efficacy of vaccination; Active Hexose Correlated Compound (AHCC) is reported to increase immunity. We have previously shown an increase in natural killer (NK) cells with supplementation of AHCC in combination with influenza vaccination in both humans and mice. We assessed changes in lymphocytes as a measure of cell‐mediated or humoral immunity, and hypothesized supplementation with AHCC would increase NK cell percentages in response to vaccination. Subjects were recruited and randomly assigned to placebo or AHCC groups in a double‐blind study, all subjects were vaccinated one week post‐supplementation. Lymphocyte populations were analyzed using BD Bioscience TBNK reagent and TruCount tubes at baseline, day of vaccination, one week post‐vaccination, and four weeks post‐vaccination. In all groups consuming 3000mg of AHCC per day, NK cell percent increased from day of vaccination to four weeks post‐vaccination. While male, female, and young populations all showed an increase in NK cell percent between 9–10% compared to placebo counterparts, elderly taking AHCC showed the greatest increase in NK cells at 14%. These results suggest AHCC can increase vaccine efficacy in all populations, but especially in elderly populations.
Reported energy intake by weight status, day and Estimated Energy Requirement among adults: NHANES 2003–2008
Authors: Brandt Kyal , Carriquiry Alicia L , Johnson LuAnn , Jahns Lisa
Published: June 2021

Objective

To describe energy intake reporting by gender, weight status, and interview sequence and to compare reported intakes to the Estimated Energy Requirement at different levels of physical activity.

Methods

Energy intake was self‐reported by 24‐hour recall on two occasions (day 1 and day 2), approximately 10 days apart. Weight status was calculated from measured height and weight. EER was calculated for each individual based on 4 physical activity scenarios, and differences in intake – EER and % of EER were calculated using a sedentary activity level. Means and differences were derived using SAS PROC SURVEY.

Results

On average, reported day 1 energy intake was 100–300 kcal higher than day 2. Comparing intake to EER calculated using a default physical activity level of “sedentary”, we see that overweight and obese groups tend to report intakes for both day 1 and day 2 that are below the calculated EER. Healthy and underweight groups tend to report intakes that are greater than the calculated EER for both days. This could be a result of dieting in the obese and overweight groups, or an increased tendency to under report intakes as BMI increases.

Source of support: National Research Initiative of the USDA Cooperative State Research, Education, and Extension Service #2007‐35215‐18102
Variety of fruit and vegetable intake and cognitive function in middle‐aged and older Puerto Rican adults
Authors: Ye Xingwang , Bhupathiraju Shilpa N , Tucker Katherine L
Published: June 2021

Higher intake of fruit and vegetable has been associated with lower risk of several chronic diseases. We examined associations between total and variety of fruit and vegetable intake and cognitive function in a cross‐sectional sample of 1412 Puerto Rican adults, aged 45–75 years, living in the Boston area. Intake of fruit and vegetables was assessed with a food‐frequency questionnaire. Cognitive function was measured with a battery of seven tests; the Mini Mental State Examination (MMSE) was administrated to assess global cognitive function. Greater variety of fruit and vegetable intake, but not total quantity, was associated with higher MMSE score after adjustment for age, sex, education, household income status, acculturation score, smoking, alcohol use, physical activity, supplement use, medication use, instrumental activities of daily living score, diabetes, hypertension, and body mass index (P = 0.02). Variety remained significant after further adjusting for quantity (P = 0.045). Higher variety of fruit and vegetable intake was also associated with better executive function, memory and attention, after adjusting for the same covariates (all P <0.05). Increasing variety of fruit and vegetable intake may be more beneficial for cognitive function in middle‐aged and older adults than just increasing total quantity. This study was supported by NIH P01AG023394, R01AG02708 and P50HL105185.
Food insecurity among households in Sidama District, Southern Ethiopia
Authors: Regassa Nigatu , Stoecker Barbara J
Published: June 2021

This study examined the level of household food accessibility/entitlement in one of the most populous zones in Southern Ethiopia, the Sidama Zone. The study used primary data collected from 1094 households with a child under 24 months of age located in nine kebeles (the smallest administrative district) selected by a multi stage probability sampling technique. The level of food accessibility was measured with the Household Food Insecurity Access Scale (HFIAS), developed by the Food and Nutrition Technical Assistance project (FANTA). This set of questions, designed to be used cross culturally, revealed that only 17.7 percent of the households were food secure. The percentages of households who were mild, moderately and severely food insecure was 6.8, 27.7 and 47.8 respectively. (Supported by Hawassa University – NORAD Project)
Anti‐obesity effect of Actiponin supplementation in obese Korean subjects: A 12 week, randomized, double‐blind, placebo‐controlled clinical trial
Authors: Park Soo‐Hyun , Back Hyang‐Im , Kim Sun‐Young , Park Eun‐Ok , Oh Mi‐Ra , Kim Min‐Gul , Choi Eun‐Kyung , Jung Su Jin , Yu Il Han , Kim Hye Mi , Huh Tae‐Lin , Cha Youn‐Soo , Chae Soo‐Wan
Published: June 2021

To investigate the effects of Actiponin, a modified extract of Gynostemma pentaphyllum plant, on anti‐obesity effect in human, we carried out 12 week, randomized, double‐blind, placebo‐controlled clinical trial for obese Korean subjects.

Obese subjects [both BMI ≥ 25 kg/m2 and WHR ≥ 0.90(men), WHR ≥ 0.85(women)] who were not diagnosed with any disease were included in this study. Eighty subjects (40.08 ± 10.60 years, 164.3 ± 8.8 cm) were randomly divided into a Actiponin (n=40, 450 mg/day) or Placebo group (n=40). Outcomes included measures of efficacy (Anthropometric parameter, abdominal fat distribution by computerized tomography, blood components) and safety (adverse events, laboratory test, electrocardiogram, and vital sign). Seventy‐four subjects (36 Actiponin group, 38 Placebo group) finished the study. After the 12 weeks of supplementation, body fat mass, body fat percent, weight, BMI (body mass index, kg/m2) in the Actiponin group was significantly reduced compared to the Placebo group (P<0.001, P<0.001, P<0.05, P<0.05). Also there was no clinically significant change of safety parameter. These results suggested that Actiponin supplementation may have positive effect on anti‐obesity.
Conservation of vestibular afferent segregation within the otolith endorgans at the striola across vertebrate classes
Authors: Mahmoud Amany Refaat , Maklad Adel Abdel Fattah
Published: June 2021

Hair cells are the basic units of transduction in the vestibular apparatus. An intriguing feature of the hair cells in the utricle and saccule is the reversal of their morphological polarity at the striola: the kinocilia of all hair cells lie toward the striola in the utricle, and away from it in the saccule. In a previous study we showed that, in mice, the striola demarcates afferent fibers projecting to the brainstem and cerebellum. We used retrograde transport of lipophilic tracers to determine whether the striola in the chick also separates afferent domains projecting to the brainstem and cerebellum. Here, we found that in the utricle, afferents projecting to the cerebellum originate lateral to the striola, whereas afferents to the vestibular nuclei in the brainstem originates medial to it. In the saccule, afferents projecting to cerebellum originate from an area superior to the striola, whereas afferents projecting to the vestibular nuclei are inferior to it. In the lagena, the cerebellar afferents originate predominantly anterior to the striola, whereas the afferents to the vestibular nuclei originate predominantly posterior to it. As in mice, these findings indicate that, the striola demarcates not only the reversal of hair cell polarity, but also the segregation of afferents to the brainstem and cerebellum. This implies a conservation of primary macular afferent pathways in several classes of vertebrates.
MyD88‐independent pathway plays an important role in alcohol‐induced osteonecrosis
Authors: OKAZAKI SHUNICHIRO , TATEDA KENJI , NAGOYA SATOSHI , KATADA RYUICHI , MIZUO KEISUKE , WATANABE SATOSHI , YAMASHITA TOSHIHIKO , MATSUMOTO HIROSHI
Published: June 2021

Objectives

Osteonecrosis of the femoral head (ONF) occurs under steroid therapy or chronic alcohol consumption. Most of patients with alcohol‐induced ONF contract alcoholic fatty liver disease, in the pathogenesis of which LPS, a ligand of TLR4, plays a crucial role. However, the pathogenesis of alcohol‐induced ONF remains unclear. In the present study, we found that feeding alcohol liquid diet for experimental alcoholic fatty liver disease causes ONF and clarified role of proinflammatory responses in the pathogenesis.

Methods

Male Wistar rats were fed Lieber DeCarli liquid diet containing 5% ethanol or dextran for 1–6 weeks. Histopathological and biochemical analyses were performed.

Results

Alcohol liquid diet feeding remarkably promoted ONF. The animal had hepatic steatosis, liver dysfunction, and hyperlipidemia as well as many previous reports. Blood IFN gamma was increased in the rat fed with alcohol liquid diet, while adiponectin levels was decreased in the rat. IFN gamma and adiponectin can be related to TLR4 understream pathways via MyD88‐independent and dependent.

Conclusions

We found ONF in the rat fed alcohol liquid diet. The animal showed elevated IFN gamma and decreased adiponectin, suggesting that IFN gamma signaling pathway may play a crucial role in the pathogenesis of alcohol‐induced osteonecrosis of the femoral head.
Radon and respiratory parameters of some secondary school students in Prizren – Kosovo
Authors: Bislimi Kemajl , Mazreku Ilir , Gashi Agim , Bahtijari Meleq , Halili Jeton , Grapci Linda , Halili Fetah
Published: June 2021

The objective of this investigation was the relationship between radon concentration level from indoor areas (classrooms) in some secondary schools of Prizren municipality and eventual consequences of ionizing radiation in the respiratory parameters of secondary school students (N=50, males and females, age 13–15 ).The measurement of radon concentration in indoor area of classrooms from different floors was made with alpha stimulating method using portable apparatus PRM‐145 and the CR‐39 detector of trace that was developed in the “Josef Stefan” Institute in Ljubljana. In the indoor air of classrooms that are located on the basement, the annual average radon concentration (222Rn) varies from 335 – 485 Bq/m3, whereas in the classrooms of other floors between 11–28 Bq/m3. Respiratory parameters were measured by the use of the method of Pulmonary Function Test. Results of the investigation show that compared with the same age group students who study in classrooms with low radon concentration; the students of classrooms with high level of radon concentration show the decreased values of respiratory parameters (tidal volume, vital capacity). The most pronounced changes of these respiratory parameters are emphasized in male students compared to female students.