bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fat flu: the obese host in influenza virus evolution
Authors: Karlsson Erik , Schultz-Cherry Stacey 
Published: June 2021

During the 2009 influenza pandemic, obesity was identified as an independent risk factor for increased disease severity and mortality. These epidemiological findings have been confirmed using obese mouse models. Previous studies in mice have demonstrated that nutritional status can affect virulence of RNA viruses including influenza. The global epidemic of obesity combined with increased disease severity in obese subjects prompted us to question whether obesity could influence influenza virus evolution. To determine if the obese lung microenvironment could differentially affect viral adaptation, A/California/04/2009 influenza virus was passaged five times in either lean or diet‐induced obese (DIO), C57Bl/6 male mice. Lean and DIO mice were then infected with parental and passaged viruses and monitored for morbidity and mortality. Interestingly, virus passaged in DIO mice induced greater morbidity, pathology and mortality in both lean and DIO animals compared to lean‐passaged virus. Studies are underway to define the molecular determinants associated with the enhanced pathogenicity; however, the obese virus retained increased pathogenicity following egg passage suggesting genetic changes to the virus itself. These studies suggest that the expanding obese population may not only be more susceptible to disease, but may differentially regulate viral evolution towards more virulent viral strains.Grant Funding Source: NIH NIAID contract number HHSN266200700005C and the American Lebanese Syrian Associated Charities (ALSAC)
Enhanced aldosterone synthesis and insufficient activation of cyp2c9‐EET pathway in the brain play a pivotal role in salt‐induced sympathetic activation in mice with pressure overload
Authors: Ito Koji , Hirooka Yoshitaka , Sunagawa Kenji 
Published: June 2021

BackgroundRecently, we demonstrated that high‐salt (HS) intake augments sympathetic drive via brain mineralocorticoid receptor (MR) – epithelial Na channels (ENaCs) pathway activation in mice with pressure‐overload (PO‐mice). In the present study, we determined whether imbalance between aldosterone synthesis and activation of cyp2c9‐EET plays a pivotal role in sympathetic activation in this model.Methods and ResultsWe performed aortic banding to create PO‐mice. Sham operation was performed as control (Sham‐mice). Four weeks after aortic banding, mice were fed with either a HS (8%) diet or a regular‐salt diet for additional 4 weeks. Urinary norepinephrine excretion, a marker of sympathetic activity was significantly increased by HS in PO‐mice, but not in Sham‐mice. The expressions of brain MR and the ratio of phosphorylated/total serum glucocorticoid inducible kinase‐1(sgk‐1), a marker of MR activity increased in PO‐mice. Furthermore, unlike in Sham‐mice, PO‐induced MR activation maintained despite HS loading. Intracerebroventricular (ICV) infusion of aldosterone synthesis inhibitor, FAD 286A (100 μg/kg/day, 4 weeks), decreased brain MR activity with the reduction of sympathetic drive. We also examined the cyp2C9 expression and 11,12‐epoxyeicosatrienoic acids (EET) concentration in the brain, a major pathway to inhibit ENaCs. HS increased cyp2c9 expression and 11,12‐EET concentration in the brain only in Sham‐mice, but not in PO‐mice.ConclusionIn PO‐mice, HS increases sympathetic drive via the activation of brain MR‐ENaCs pathway through aldosterone‐dependent MR activation and insufficient activation of cyp2c9‐EET pathway.
The shape, size, and asymmetry of fetal hippocampal formation during the second trimester: A 7.0 Tesla postmortem MRI study
Authors: Liu Shuwei , Liu Jun , Zhang Zhonghe , Teng Gaojun , Fang Fang , Zang Fengcao 
Published: June 2021

ObjectiveThe purpose of this study is to find morphometric changes of the HF during the second trimester.Material and methods46 fetal specimens with gestational ages(GA) of 13–22 weeks were scanned with a Bruker 7.0T MR Scanner. The MR image data were analyzed and post‐processed with Amira 4.1. Three‐dimensional structures were produced and volumes of the labeled HF were calculated.ResultsWith 7.0T MRI, some morphological appearances were delineated. Before 16 to17 weeks, the HF is just a flat structure. Then, the HF becomes cylindrical structure with an impressive hippocampal sulcus. The left and right hippocampuses demonstrated significant increases in volume with gestational age (Left: R=0.8663, Right: R=0.889). The two side HF volumes were tested by Wilcoxon signed‐rank test. The right HF was larger than the left one.ConclusionDuring the period, the volume growth of HF is a significantly positively correlated with age in weeks and there is asymmetrical growth in volume.
Bioactive Nanomaterials for Enhanced Wound Healing
Authors: Balkawade Rohan Sambhaji , Mills David Keith 
Published: June 2021

Wound healing has become a significant problem for patients, doctors and the US health care system, affecting millions of people and costing billions of dollars. Several biodegradable and non‐toxic materials are under research to develop a biomolecular environment for wounds that will enhance the healing process. One of the methods is developing a polyelectrolyte nanofilm multilayer's (PNMs) as a nanocoating on the surface of the wound embedded with growth factors. The PNMs is developed using an ultrasonic nebulizer (UN) by spraying oppositely charged polyelectrolytes over the skin (Epiderm full thickness which is a human skin equivalent). By using UN we can control rate of deposition/concentration, time, and thickness of PNMs. Oppositely charged, Poly‐L‐Glutamic acid (PGA) and Poly‐L‐Lysine (PLL) served as a basic architecture for the nanofilm in which platelet derived growth factor (PDGF‐B) and insulin like growth factor (IGF‐1) were incorporated in deep (D), double (DL), and combined layer (CL). PNMs embedded with PDGF and IGF showed increased epithelization, connective tissue formation, and collagen deposition when compared with the controls. These results suggest that PNMs act as a bioactive and biodegradable drug delivery system to enhance the wound healing process.Research support: Governor's Biotechnology Initiative.
Interferon Regulatory Factor 6, a novel transcriptional regulator of embryonic development and wound healing
Authors: Biggs Leah C , Le Mark , Rhea Lindsey , Kinoshita Akira , Murray Jeff C , Schutte Brian C , Dunnwald Martine 
Published: June 2021

Cleft lip and palate (CLP) constitutes the second most common congenital birth defects in the US. This complex trait results from a disruption of the highly coordinated growth, migration and fusion of facial prominences during early embryological development. Evidence from genetic studies, animal models, and expression data suggest a variety of candidate genes for CLP. Amongst them, Interferon Regulatory Factor 6 (IRF6) is unique because DNA variation in this gene both causes and contributes significant risk for orofacial clefts. IRF6. Loss of function of IRF6 in human causes two orofacial syndromes, Van der Woude (VWS) and Popliteal Pterygium. In the mouse, deletion of Irf6 leads to craniofacial anomalies, as well as limb and cutaneous defects. These data support a role for Irf6 in embryonic development. Recent clinical chart review of patients with orofacial clefts indicated that patients with VWS were more likely to develop wound complications after corrective cleft surgery compared to patients with an isolated cleft, suggesting that IRF6 plays an additional role in wound healing. We took advantage of the murine model to culture keratinocytes from wildtype and Irf6‐deficient animals. Our in vitro data indicate a delay in scratch closure in the absence of Irf6. Potential molecular mechanisms beyond this observation will be presented, along with novel in vivo wound healing models.DE16215 and AR055313
Changing the Course of America Through Mentoring
Authors: Jones Lovell Allan 
Published: June 2021

Over forty years ago, as a new director of the National Institute of General Medical Sciences, Dr. Ruth Kirschstein formed a partnership with Dr. Geraldine Woods and Congressman Louis Stokes to create two ground breaking program, The Minority Biomedical Research Support Program (MBRS), and later, the Minority Access Research Careers (MARC). These stellar programs were the foundation programs to diversify science in America. Yet, forty years later, we are still taking about diversifying science. When I was informed that I was the 2012 Ruth Kirschstein Diversity in Science Honoree, I wonder what she and Dr. Woods would say today about the status of diversity in Science in America. Why has these programs been both successful in raising the numbers, but unsuccessful in changing the landscape of science in our academic institutions. That will be focus of my presentation. The focus will also be on a least one option we should pursue.In 2002, I realized that I was mining a depleted field. I was taking the survivors of the K – 12 battleground and not enriching the number of underserved students we lose between K ‐ 12. Not changing the fact that we lose between 80 to 85% of our kids interested in science between the 3rd and 4th grade. The object of The Science Centered Inquiry‐Based Educational Activities iN Collaborating Elementary Classrooms (SCIENCE) Project, our early childhood educational component of the PIPELINE Program, is to develop a model to reverse this lost that can be replicated. To link this program with other components of the pipeline that makes science exploration relevant to the underserved. Not that all of these students will become physicians, other health care providers or scientists, but at least they will form the basis for a science education populous.
Hormonal and cellular control of hepatic lipid metabolism
Authors: Rutter Jared 
Published: June 2021

We are interested in the mechanisms whereby the body senses its nutrient environment and responds to adapt cellular and organismal metabolism to this changing environment. One maladaptive response to excess feeding is excess fat storage driven by the Sterol Response Element Binding Protein‐1c (SREBP‐1c) transcription factor. SREBP‐1c is activated at multiple levels in response to insulin signaling and stimulates the expression of the entire de novo lipogenesis and triglyceride biosynthesis program. The signaling pathway whereby insulin stimulates SREBP‐1c activity includes the canonical PI3K‐Akt module, but has recently been shown to also depend on the Akt‐dependent activation of the mTOR Complex 1 (mTORC1). We have recently characterized a novel component of this pathway that sheds additional light on how feeding‐induced lipogenesis is controlled.PAS kinase (PASK) is a highly evolutionarily conserved protein kinase that we have shown to be metabolically regulated and to control glucose‐responsive processes in pancreatic beta‐cells. A mouse lacking PASK, in addition to modest beta‐cell defects, has a profound resistance to the pathological effects of a high‐fat diet. Specifically, PASK−/− mice are protected from the obesity, insulin resistance and dyslipidemia observed in wild‐type mice on a high‐fat diet. The most striking effect that we observed was a loss of the massive hepatic lipid accumulation that occurs on a high‐fat diet. This was accompanied by decreased expression of many of the genes that promote lipid uptake and synthesis in the liver. We demonstrated that PASK strongly regulates SREBP‐1c in cultured cells using a combination of loss‐of‐function and gain‐of‐function approaches and genetics, cell biology and biochemistry. Based on these observations in vitro, we went back to the mouse model and showed that, indeed, the entirety of the SREBP‐1c transcriptional program was decreased in PASK−/− mice. Our preliminary data suggests that PASK regulates SREBP‐1c at the level of proteolytic maturation.In parallel, we observed that PASK was strongly activated post‐translationally by insulin and that mTORC1 activation was necessary and sufficient for this effect. The current evidence suggests that mTORC1 activates PASK through direct interaction with and phosphorylation. Having found that insulin/mTORC1 activates PASK and PASK activates SREBP‐1c, we then tested whether PASK is a required mediator of the acute insulin/mTORC1 effects on SREBP‐1c and found that it is. My laboratory is now focused on understanding the mTORC1‐PASK‐SREBP‐1c pathway, both the mechanisms of signal transduction and the physiological importance of this pathway.
Pilot Study on the Management of Childhood Overweight: A Pound of Cure
Authors: Anzeljc Samantha Ann , Murray Robert 
Published: June 2021

Primary care clinicians (PCCs), despite regular access to families with young children, lack a cohesive model for approaching office visits regarding excess weight. Using the 2007 Expert Committee's Recommendations, a set of clinician guidelines on the standard of care for managing childhood obesity, we developed high quality intervention tools for PCC use to direct behavior modification in families with children 2 to 11 years old. We piloted modularized counseling sessions with accompanying educational handouts. To date, we have interviewed 77 families on the counseling sessions and resources. The feedback we obtained guided development of office visit modules and of parental educational materials. On average, motivated families that returned to the clinic needed to complete only 3 to 4 modules, setting 3 goals per visit, to successfully incorporate recommendations into the child's daily life. Of families that returned for follow up visits 41.5%, 37.7%, 13%, and 5.2%, of families completed 2, 3, 4, or 5 office visits respectively. Additionally, of families that attended follow up visits 50%, 37.9%, 60% and 75% of children reduced their BMI percentile as they attended the 2nd, 3rd, 4th, and 5th office visits, respectively. In total, 47% of children attending office visits have either maintained or reduced their BMI.Grant Funding Source : Medical Mutual of Ohio
ApoER2‐Mediated Endocytosis of Long‐Isoform Selenoprotein P (Sepp1) Supplies Skeletal Muscle Cells with Selenium
Authors: Kurokawa Suguru , McDonald W. Hayes , Hill Kristina E. , Burk Raymond F. 
Published: June 2021

Sepp1 transports selenium from the liver to tissues such as testis, brain and kidney. Apolipoprotein E receptor‐2 (apoER2) and megalin, both members of the low‐density lipoprotein receptor (LDLR) family, have been identified as Sepp1 receptors in those tissues. The mechanism of selenium acquisition by skeletal muscle cells is not known. We studied selenium uptake by a rat myoblast cell line. L8 cells took up Sepp1 from the medium and utilized its selenium for the synthesis of glutathione peroxidase (Gpx). However, L8 cells did not take up Gpx3 or the Sepp1 isoform that lacked the selenium‐rich C‐terminal domain. To identify Sepp1 receptors on L8 cells, a solubilized membrane fraction from them was passed over a Sepp1 column. ApoER2 and Lrp1, another LDLR family member, were identified in the column eluate by mass spectrometry. RNAi experiments showed that knockdown of apoER2 inhibited 75Se uptake from 75Se‐labeled Sepp1 while knockdown of Lrp1 had no effect on it. Inhibition of clathrin‐mediated endocytosis suppressed 75Se uptake. Blocking of lysosome acidification did not inhibit uptake of 75Se from 75Selabeled Sepp1 but it suppressed development of Gpx activity by blocking digestion of the endocytosed Sepp1. We conclude that long‐isoform Sepp1 binds apoER2 on L8 cells and is endocytosed and digested in lysosomes to provide selenium to the cells. Supported by NIH grants ES02497 and DK82813.Grant Funding Source: NIH
PNPLA3 Gene Expression is Regulated by Carbohydrates and Unsaturated Fatty Acids in vitro and in vivo
Authors: HAO LEI , Ito Kyoko , Wray Amanda E , Mueller Natalie M , Atluri Mokshasree , Ross Catharine A 
Published: June 2021

A polymorphism of the patatin‐like phospholipase‐3 (PNPLA3, adiponutrin) gene is strongly associated with non‐alcoholic fatty liver disease. However, the functions of PNPLA3 are not well understood. To examine mechanisms by which nutrients regulate PNPLA3 gene expression, C57BL/6 male mice were fed a normal chow diet (control), a high‐carbohydrate liquid diet, or the same diet with lipid emulsion for 4 weeks. PNPLA3 gene expression was increased ~22‐fold in the high‐carbohydrate diet fed group compared to the control group. However, lipid emulsion completely reversed PNPLA3 induction by the high carbohydrate diet. In HepG2 cells that were cycled between 5.5 and 25mM glucose (starvation and refeeding conditions), PNPLA3 was significantly decreased ~5‐fold by glucose starvation and increased ~2.5‐fold by glucose refeeding, while insulin had no effect. Carbohydrate response element binding protein (ChREBP) expression correlated with PNPLA3 expression. Unsaturated fatty acids, oleic acid and linoleic acid (400 μM, 24 h), each significantly decreased PNPLA3 mRNA by ~50%, but linolenic acid did not, although Oil Red O staining was similar for all fatty acids. We conclude that PNPLA3 is regulated by carbohydrates and certain types of unsaturated fatty acids both in vitro and in vivo, and suggest a role for PNPLA3 in lipogenesis. (NIH CA‐ 90214)Grant Funding Source : NIH CA‐90214
Activation of brown adipose tissue by acute and chronic administrations of capsinoids in humans
Authors: Yoneshiro Takeshi , Aita Sayuri , Matsushita Mami , Saito Masayuki 
Published: June 2021

ObjectiveCapsinoids, nonpungent capsaicin‐related substances, are known to increase brown adipose tissue (BAT) thermogenesis and whole‐body energy expenditure (EE), and reduce body fat in small rodents. The objective of this study was to clarify whether BAT is involved in the thermogenic effects of capsinoids in humans.ResultsEighteen male volunteers underwent fluorodeoxyglucose‐ positron emission tomography after 2‐h cold exposure at 19 °C, and were divided into BAT‐positive and ‐ negative groups. Thermogenic responses to orally ingested capsinoids (9mg) or placebo were examined by indirect calorimetry at 27 °C. Thermogenic responses to cold at 19 °C (CIT) were also examined before and after daily ingestion of capsinoids for 6 weeks.ResultsOral ingestion of capsinoids increased EE in 1 h by 15.2 ± 2.6 kJ/h in the BAT‐positive group, more than in the BAT‐negative group (1.7 ± 3.8 kJ/h). Placebo ingestion produced no significant change in either group. CIT in the BAT‐negative group was much lower than that in the BAT‐positive group, but it increased after 6‐week capsinoids ingestion.ConclutionsOral ingestion of capsinoids increases EE by stimulating and recruiting BAT in humans.
Carbohydrate restriction favorably affects HDL metabolism in men and women with Metabolic Syndrome. Addition of egg yolk further increases large HDL particles
Authors: Andersen Catherine J , Blesso Christopher N , Park Youngki , Barona Jacqueline , Pham Tho , Lee Jiyoung , Fernandez Maria Luz 
Published: June 2021

We investigated the effects of carbohydrate restriction (CR) and whole egg consumption on HDL‐cholesterol (HDL‐C), HDL particle size/diameter, and peripheral blood mononuclear cell (PBMC) ATP‐binding cassette transporter A1 (ABCA1) mRNA expression in men and women (n=18) classified with Metabolic Syndrome (MetS). Participants followed a carbohydrate‐restricted diet (25–30% carbohydrate) in addition to daily consumption of either 3 eggs (EGG group) or the equivalent amount of egg substitute (SUB group) for 12 wk. All participants decreased body weight (p < 0.001) and BMI (p < 0.001) over time with no differences between groups. There were also increases in plasma HDL‐C (P < 0.010) over the 12 wk, whereas no changes were observed in either plasma total or LDL‐cholesterol despite greater daily cholesterol intake by the EGG group (p < 0.001). Decreases in body weight and BMI correlated with increases in mRNA expression of ABCA1 (r = −0.587; p< 0.025 and r = −0.579; p< 0.025, respectively). In addition, changes in ABCA1 mRNA expression highly correlated with changes in HDL size (r = 0.763, p= 0.001). There was an increase in both the number of HDL particles and large HDL over time with greater increases in the EGG group (P< 0.05). All participants also had decreases in the atherogenic medium‐sized HDL particle (p< 0.01). These studies support the role of CR and whole egg consumption in improving HDL metabolism in people with MetS.Grant Funding Source: Egg Nutrition Center
EGCG protects against 6‐OHDA induced neurotoxicity in a cell culture model
Authors: Chen Dan , Kanthasamy Anumantha G , Reddy Manju B 
Published: June 2021

Disruption of iron metabolism may involve in the progression of Parkinson's disease. Our objective was to test whether the protective effect of (−)‐epigallocatechin‐3‐gallate (EGCG) against 6‐hydroxydopamine (6‐OHDA) induced neurotoxicity was by regulating iron homeostasis in N27 cells. EGCG pretreatment significantly protected against 6‐OHDA‐induced neurotoxicity (MTT, SYTOX Green and Caspase‐3 activity assays). EGCG with 6OHDA treatment significantly increased (p<0.0001) TH+ cell count (3.1‐fold) and neurite length (12.5‐fold) compared with 6‐OHDA alone in primary mesencephalic neurons. 6‐OHDA treatment significantly (p<0.05) increased divalent metal transporter‐1 (DMT1), hepcidin, transferrin receptor‐2 (TfR2), H‐ferritin and decreased ferroportin‐1 (Fpn1), TfR1 mRNA expressions. The protein expressions of DMT1, hepcidin and Fpn1 matched with the gene expression data. However, EGCG significantly reversed the effect of 6‐OHDA on above genes and proteins expression. The increased ~2‐fold (p<0.001) 55Fe cell uptake with 6‐OHDA and normalization with EGCG pretreatment confirmed iron burden associated with neurotoxicity and protection by EGCG. In conclusion, EGCG protected against 6‐OHDA induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis. However, further studies are warranted to determine the mechanism of that regulation.Grant Funding Source : Nutrition Wellness and Research Center
Trends in sources of empty calories for 2–18 year olds in the US: 1977–2008
Authors: Slining Meghan M , Popkin Barry M 
Published: June 2021

Much emphasis is placed on reducing consumption of empty calories from added sugars and solid fats. Our objective was to study 30‐year trends in food and beverage sources of empty calories among US 2–18 year olds. One day of nationally representative dietary intake data for each period was examined. We categorized foods with excessive added sugars (≥13% of energy from added sugars), excessive saturated fat (≥9.1% of energy from saturated fat) or both as key sources of empty calories. All analyses use sample weights that reflect the US population aged 2–18 y. The percent of energy consumed by children and adolescents from foods and beverages classified as empty calories remained stable from 1977–2005 (80% of total energy from empty calorie foods), with a slight decrease to 76% by 2008. A concurrent decrease it total calories consumed was observed over the same time period (2003–2008). While per capita consumption decreased, the top sources of empty calories remained consistent across time, namely sugar sweetened beverages, excess fat pizza, excess fat milk beverages, excess fat processed meats, excess fat pasta dishes, excess fat poultry and excess fat cakes, cookies and pies. Substantial increases in intake were observed from 2003‐ 2008 for excess fat tortilla based dishes and cheese. These findings provide important insights on recent improvements in child diet as well as areas that can still be enhanced.Funding comes from the Robert Wood Johnson Foundation (Grant 67506).