bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pericytes promote angiogenesis at the early stage of wound healing
Authors: Morikawa Shunichi , Ezaki Taichi 
Published: June 2021

Recently, more and more attention has been focused on pericytes as a target of anti‐angiogenic therapy. In this study, we sought to determine whether they exist at the early stage of angiogenesis, and if they existed, determine how they function at this stage during wound healing. In wound tissue, NG2 proteoglycan and desmin immunoreactive pericytes were closely associated with newly forming blood vessels that contained endothelia with BrdU incorporated proliferative cell nuclei. These pericytes co‐expressed vascular endothelial growth factor ‐A (VEGF‐A). Association of pericytes on the migrating/sprouting endothelia with mitotic figure was also observed with transmission electron microscopy. Phenotypically, the pericytes in wound tissues had larger cell bodies and more euchromatic nuclei than the pericytes in normal vasculature, and expressed alpha smooth muscle actin in general, which is unusual phenomenon especially in normal capillary pericytes. These observations together indicate that the activated state of pericytes is essential for the angiogenesis at the early stage of wound healing.We conclude that pericytes do exist at the early stage of the angiogenesis during wound healing to induce proliferation of endothelia and to guide their migration/sprouting via VEGF‐A secretion, though the generally accepted view suggests the absence or disappearance of pericytes at this stage of angiogenesis.
Cytotoxicity and efficacy evaluation of polymeric nanoparticles containing resveratrol and quercetin for use on drug eluting stents
Authors: Kleinedler Jim , Foley John , Dugas Tammy 
Published: June 2021

Current generation coronary drug‐eluting stents (DES) used to treat restenosis are associated with unintended complications including potentially fatal late‐term thrombosis and hypersensitivity reactions. This provides a platform for novel engineered device therapies that exhibit increased biocompatibility and promote vascular healing after angioplasty. Resveratrol and quercetin have antimitogenic actions on vascular smooth muscle cells (VSMC) and inhibit both platelet and inflammatory cell activation. Our aim was to develop a stent coating that releases these drugs within a therapeutic range and provides an extended release profile to inhibit cascades responsible for restenosis and thrombosis. Stainless steel flats were coated with arborescent polyisobutylene‐polystyrene polymer (arbIBS) applied using the novel NanoElectrospray(TM) process. To determine DES‐mediated effects, assays were conducted on flats incubated in transwells in the presence of vascular cells. These included measures of cell viability, platelet activation, and cell proliferation. Results from this study indicate that arbIBS exhibits no cytotoxicity, and that the nanoparticles release resveratrol and quercetin at the therapeutic level, reducing platelet activation and VSMC proliferation. Ongoing experiments are aimed at introducing these DES into an animal model of angioplasty for further evaluation.Grant Funding SourceR01‐HL082472
Regulation of BRCA‐1 by Xenobiotic and Dietary Ligands of the Aryl Hydrocarbon Receptor
Authors: Papoutsis Andreas J , Romagnolo Donato F 
Published: June 2021

The BRCA‐1 protein is involved in repair of DNA damage and mutations of the BRCA‐1 gene confer a high risk of developing breast cancer. Interestingly, mutations of BRCA‐1 account for only 5‐10% of breast cancer cases, whereas sporadic breast tumors represent the remaining 90‐95%. In sporadic breast cancers there is silencing of BRCA‐1 in the absence of mutations. Factors contributing to this etiology include the environmental ligands of the aryl hydrocarbon receptor (AhR) 2,3,7,8 tetrachlorodibenzene(p)dioxin (TCDD) and polycyclic aryl hydrocarbons (PAHs). Dietary antagonists of the AhR with potential protective effects include the phytoalexin resveratrol and 3,3′‐diindolylmethane (DIM), the condensation product of indole‐3‐carbinol. The objective of this study was to investigate the mechanisms responsible for repression of BRCA‐1 expression by the activated AhR. Results of DNA binding studies in MCF‐7 breast cancer cells documented that TCDD‐induced the association of the AhR to xenobiotic responsive elements (XRE) harbored in the BRCA‐1 promoter region. The cotreatment with resveratrol (5, 10, 20µM) reduced AhR recruitment in a dose‐dependent fashion. We are investigating the chromatin modifications induced by the AhR at the BRCA‐1 gene and the preventative effects of resveratrol. These studies may have implications for the use of dietary AhR ligands in prevention of BRCA‐1 silencing induced by AhR agonists.Grant Funding SourceSusan G. Komen Breast Cancer Foundation and Arizona Biomedical Research Commission
Induction of Cellular Senescence and DNA Damage Response by Selenium Compounds
Authors: Wu Min , Lartey Fred , Schoene Norberta W , Cheng Wen‐Hsing 
Published: June 2021

Although selenium chemoprevention by apoptosis has been well studied, it is not clear whether and how other tumorigenesis barriers participate in selenium chemoprevention. To address this issue, we treated MRC‐5 normal lung fibroblasts with 0‐10 µM sodium selenite, 0‐10 µM methylseleninic acid (MSeA) and 0‐500 µM methylselenocysteine (MSeC) for 48 hours, followed by a recovery of 1‐7 days. There is a selenium dose‐dependent decline in cell survival during the time course. To determine whether senescence response can be induced by sub‐lethal doses of the selenium compounds, we measured senescence‐associated expression of â‐galactosidase (SA‐â ‐gal) and bromodeoxyuridine (5‐bromo‐2‐deoxyuridine, BrdU) incorporation. We observed increased SA‐â ‐gal staining and decreased incorporation of BrdU into the replicative DNA after cellular exposure to the selenium compounds. In response to clastogens, ATM is rapidly activated, which in turn initiates a cascade of DNA damage response including histone H2AX phosphorylation at Ser‐139 (also known as ãH2AX). Results from Western analysis demonstrated increased expression of phosphorylated‐ATM and ãH2AX after the selenium treatment. Taken together, the results suggest a novel mechanism of selenium chemoprevention by which selenium induces DNA damage response and senescence to inhibit tumorigenesis.Grant Funding SourceN/A
Use of the World Health Organization (WHO) growth standards to evaluate prevalence and predictors of overweight in preschool children enrolled in the WIC program
Authors: Maalouf Zeina , Metallinos‐Katsaras Elizabeth , Dewey Kathryn G 
Published: June 2021

With the current childhood obesity epidemic, tools for accurate diagnosis of childhood obesity are needed. The World Health Organization (WHO) issued new growth standards for children under five that differ considerably from the 2000 Centers for Disease Control and Prevention (CDC) growth charts. We used records of 143,792 children aged 2‐5 years who participated in the Massachusetts Special Supplemental Nutrition Program for Women, Infants and Children from 2001‐06 to compare the prevalence and predictors of childhood overweight using the WHO vs. the CDC cut‐offs. The prevalence of overweight (>95th percentile) was 17.0% using the CDC cut‐offs vs. 23.6% using the WHO cut‐offs; the difference was largest in children 24‐27 mo of age (12.7% vs. 25.4%, respectively). In a logistic regression model controlling for birth weight and child age, factors significantly related to child overweight, assessed using the WHO cut‐offs, were maternal pre‐pregnancy weight (obese vs. normal OR=1.81 (1.72‐1.91)), Hispanic ethnicity (OR=1.50 (1.43‐1.56, ref=non‐Hispanic), maternal education (some college vs. less than high school graduate (HS), OR=0.80, 0.75‐0.85, HS vs less than HS OR=0.90, 0.86‐0.94) and child sex (OR=0.89, 0.85‐0.93, ref=male). Using the WHO charts will result in a higher estimated prevalence of childhood overweight and allow for earlier diagnosis, thus making earlier intervention possible.Supported by a grant from the United States Department of Agriculture Economic Research Service Research Innovation and Development Grants in EconomicsGrant Funding SourceUnited States Department of Agriculture Economic Research Service Research Innovation and Development Grants in Economics
Diet quality, anthropometric status and self‐reported chronic diseases among Mexican households
Authors: Xochitl Ponce Martínez , Lucia Hernánez Barrera , Simón Barquera Cervera 
Published: June 2021

ObjectiveTo evaluate association between diet quality and cardiovascular diseases among Mexican households.MethodsA secondary analysis from the MxFLS was conducted in 8840 Mexican families. Dietary quality was evaluated considering adherence to WHO dietary recommendations. Households were classified in 4 groups according to their anthropometric status. Self‐reported health information was used to identify nutrition‐related chronic diseases. The association between type of HH and NRCD was analyzed using logistic regression models.ResultsUnderweight HH reported a significantly higher consumption of fiber. Overweight HH reported significantly higher intakes of total and saturated fat and cholesterol. HH who reported a NRCD showed the lowest adherence to the recommendation of fruit and vegetables intake. Overweight HH were 2.8 times more likely to report DM and 2.27 likely to report hypertension. Double burden families reported 2.27 times more probability of presenting hypertension.ConclusionsLack of adherence to WHO recommendations with regards to saturated fatty acids and cholesterol, as well as fruits and vegetables, could be considered risk factors for development of chronic disease in overweight and double burden HH in Mexico.
Food insecurity is associated with iron deficiency anemia in U.S. adolescents
Authors: Eicher‐Miller Heather A , Mason April C , Weaver Connie M , McCabe George P , Boushey Carol J 
Published: June 2021

Food insecurity is a problem faced by many Americans. This condition is associated with decreased intake of nutrients and poor health. Food insecure children are especially vulnerable. Inadequate iron in the diets of food insecure children could eventually lead to iron deficiency and iron deficiency anemia. The purpose of this study was to formally investigate the current relationship of iron status and food insecurity in children. Child participants ages 1 to 19 years (n=12,329) of the recently released NHANES 1999‐2004 were classified as food secure or food insecure using the U.S. Children's Food Security Scale and the U.S. Household Food Security Module. Two or more abnormal values for transferrin saturation, serum ferritin, and erythrocyte protoporphyrin were used to classify iron deficiency with the addition of low hemoglobin to classify iron deficiency anemia. Results indicated that the odds of iron deficiency anemia were 2.61 times more likely (P=0.029) among food insecure children 12 to 15 years compared with food secure children. The results of this study indicate a continuing need for successful interventions to improve iron deficiency and iron deficiency anemia among food insecure children.Source of Financial Support: Purdue University Extension
Losartan affects Tyrosine Hydroxylase Protein Expression in the A2 Area and Hypoglossal Nucleus of Normal and Dystrophic Hamsters
Authors: Ambur Lindsay Christen , Schlenker Evelyn Heymann 
Published: June 2021

Angiotensin AT1 receptors affect production of tyrosine hydroxylase (TH), the rate‐limiting enzyme for production of catecholamines. AT1 receptors are colocalized with TH in the A2 region of the nucleus tractus solitaries and hypoglossal nucleus. We hypothesized that blocking AT1 receptors with losartan (L), an AT1 receptor antagonist, would decrease TH expression in the A2 and hypoglossal nucleus in normal (N) and dystrophic (D) hamsters. Two month old male N and D hamsters received tap water or L in drinking water at a dose of 50 mg/kg/day for 2.5 months. At 4.5 months, animals were sacrificed, brains perfused, cryoprotected, and frozen at ‐70° C. Brains were sliced at 35‐40 micrometers. Immunohistochemistry was performed using a mouse monoclonal TH primary antibody (1:10,000) visualized with DAB. ImageJ was used to evaluate A2 and hypoglossal areas and number of TH positive neurons. Losartan had no effect on hypoglossal areas, but decreased the number and density of TH positive neurons and in D hamsters, but not in N hamsters. In N and D hamsters TH positive neurons were predominately located in ventral regions of the hypoglossal nuclei. Losartan treatment eliminated this localization in both groups. In the A2 region no significant differences were observed in areas or number of positive TH neurons, but in D hamsters L decreased TH positive neuron density.Funded by: APS Undergraduate Summer Fellowship & P20 RR‐015567
Regulation of calcium transport by the mammalian retinal pigment epithelium
Authors: Echtenkamp Stephen F. , Kennedy Brian G. , Mangini Nancy J. 
Published: June 2021

The retinal pigment epithelium (RPE) is a transporting epithelial monolayer that regulates the composition of the subretinal space bathing the photoreceptor outer segments. Calcium concentration in the subretinal space varies with illumination of the retina. In this study we characterized the transepithelial calcium transport by the mammalian RPE. By immunocytochemistry we localized plasma membrane calcium transport proteins PMCA, TRPV5 and NCX to both apical and basolateral RPE membranes in bovine or human native tissues. Calcium transport activity was assessed as transepithelial 45‐Ca flux in voltage‐clamped bovine RPE/choroid Ussing preparations. Apical‐to‐basal and basal‐to‐apical Ca fluxes were measured in both short and open circuit conditions. We found that bovine RPE/choroid catalyzes a net, active calcium transport in the basal‐to‐apical (choroid‐to‐retina) direction. In normal open circuit condition, the positive apical transepithelial potential drives a paracellular calcium flux that roughly balances this active transport. Application of low sodium Ringer solution to the apical surface decreased net basal‐to‐apical flux by almost 90%, suggesting that NCX activity contributes to the active transepithelial calcium transport in bovine RPE.Supported by American Health Assistance Foundation, Macular Degeneration Research
Regulation of stromelysin‐2 in inflammation
Authors: Chen Ann J , Birkland Timothy P. , Chen Peter , Altemeier William A. , Parks William C. , McGuire John K. 
Published: June 2021

IntroductionSpecific members of the matrix metalloproteinases (MMPs) family are key mediators of inflammation. Our preliminary data suggest stromelysin‐2 (MMP‐10) also functions to moderate inflammation. Stromelysin‐2 is not found in healthy tissue but is highly induced in injured epithelium. However pathways controlling stromelysin‐2 up‐regulation in inflammatory processes are not known.DataWe found high levels of stromelysin‐2 gene expression in various models of lung injury, including mice challenged with Pseudomonas aeruginosa, influenza, and bleomcyin. We found mice lacking stromelysin‐2 had increased lung injury and higher mortality in response to P. aeruginosa. Bioinformatic analysis of the five kilobase region upstream of the gene identified several binding regions essential to stromelysin‐2 gene regulation.ConclusionWe conclude that increased expression of stromelysin‐2 is a generalized protective host response in inflammation. We report several transcription factor binding sites responsible for the regulation of stromelysin‐2 in inflammation.This research is supported by grants from the American Lung Association and the National Institute of Health (HL029594, HL077555).
A re‐examination of the striated organelle in vestibular endorgans
Authors: Vranceanu Florin , Lysakowski Anna 
Published: June 2021

The striated organelle (STO) is a structure located in the subcuticular region of hair cells, consisting of alternating thick and thin bands. Although present in all cochlear and vestibular hair cells, the STO is particularly well‐developed in type I hair cells, where it is shaped like an inverted open ended cone that contacts the cell membrane along its entire circumference and is separated from the cuticular plate by a layer of mitochondria. In other hair cells, it is a much smaller structure and appears to be free‐floating. We studied its structure in EM tomography of the type I hair cell. In three‐dimensional reconstructions, we found that it is connected to at least some actin rootlets. It may also be associated with microtubules, mitochondria and smooth ER. Confocal immunohistochemistry places Yotiao (an AKAP protein) in the same area as the STO and the actin‐binding protein, alpha fodrin (non‐erythroid spectrin), where the STO contacts the cell membrane. The contact with the rootlets suggests that the STO might regulate hair‐bundle stiffness. Its association with the cell membrane suggests that the STO may help in the formation of the constricted neck characteristic of type I hair cells.Supported by NIH DC‐02521 and the 2008 Tallu Rosen Grant in Auditory Science (from the National Organization for Hearing Research Foundation)Grant Funding SourceNIH DC‐02521; 2008 Tallu Rosen Grant in Auditory Science (NOHR)
Labeling of inner ear afferents in the transgenic thy1‐YFP‐H mouse
Authors: Chidavaenzi Robstein Lovejoy , Lysakowski Anna 
Published: June 2021

We wished to assess the level of inner ear endorgan labeling in a transgenic mouse expressing yellow fluorescent protein (YFP) driven by the thy1 promoter and to examine the possibility of using this thy1‐YFP‐H mouse as a model for studying inner ear afferents. End‐organ YFP fluorescence in a postnatal day 8 (P8) thy1‐YFP‐H mouse was observed using confocal microscopy after anesthetizing the animal, then transcardially perfusing it with PBS and 4% paraformaldehyde. Images from utricular and cochlear whole mounts and crista sections suggest that in the thy1‐YFP‐H P8 mouse, vestibular afferents, including both calyces and boutons and type I and II spiral ganglion afferents are labeled. Afferents in the striolar region were more intensely labeled than extrastriolar afferents, and no supporting cell labeling was observed. Cochlear afferents, including those innervating both inner and outer hair cells, were also labeled. In conclusion, the thy1‐YFP‐H mouse could be a useful model in which to study inner ear endorgan structure and function as it lends itself to in‐vivo imaging and enables easy identification and distinction of afferent types and regions.Supported by NIH DC‐02521.Grant Funding SourceNIH DC‐02521
GDP‐mannose transporter contributes to polarity establishment in the filamentous fungus Aspergillus nidulans
Authors: Johnson Laura , Gordon Barbara , Groover Chassidy , Martin Stuart , Hill Terry , Loprete Darlene , Jackson‐Hayes Loretta 
Published: June 2021

GDP‐mannose transporters (Gmt) carry nucleotide sugars from the cytosol across the Golgi apparatus membrane in various eukaryotic organisms including plants and a variety of fungi. Some fungal species such as the yeast Saccharomyces cerevisiae express only one Gmt, while others including A. nidulans express paralogues (GmtA and GmtB) whose individual roles have not been elucidated. As in S. cerevisiae GmtA is localized within the Golgi apparatus which in A. nidulans consists of widely separated cisternae, in contrast to the stacked cisternae of animals and plants. Here we show that GmtB localization is congruent with GmtA in mature hyphae. Real‐time reverse transcriptase PCR shows a gradual decrease in GmtA expression during the first 12 hours of germination while GmtB expression remains high and unchanged during this period. Depletion of GmtB by the glucose repressible alcA promoter causes abnormalities in polarized growth, a developmental event that is initiated during the early hours of germination. Taken together these observations suggest that GmtB plays an important role in establishment of polarized growth. Although GmtA and GmtB reside within the same Golgi compartments they appear to perform independent functions at different developmental stages.Funded by Research Corporation, the Merck/AAAS Undergraduate Science Research Program and NSF RUI
A Biochemical Driver for Living Systems: the Proton Pump
Authors: Haines Thomas H. 
Published: June 2021

All living membranes (as apposed to myelin, a non‐living membrane) pump protons or other ions. The introduction of the sources of energy upon which living cells rely, enter cells via ion, commonly proton, pumping to make ATP. These energy sources consist of either redox energy or photons. Heterotrophic cells may take in energy in the form of glucose or other covalent bond sources, but the energy is converted into NADH or its equivalent by metabolism. The reductive product is then transduced via proton pumping to ATP production. In eukaryotes some of that ATP may be used thereafter to pump protons in other, internal cellular membranes.Thermodynamically, living cells characteristically use energy to create order. The equations that explain this apparent contradiction of the 2nd Law of Thermodynamics were best derived by Ilya Prigogene and Ephraim Katchalsky who established that such activities must be near‐to‐equilibrium and must be local within a larger surrounding environment that increases the entropy. Prigogene showed that although local, near‐to‐equilibrium systems may be interlocked. Thus, for example, if the act of proton pumping were reversibly connected to ATP synthesis, the ATP could then be used as a key component of other near‐to‐equilibrium systems such as metabolism and/or cytoskeletal activities.I propose a specific mechanism for the act of proton pumping that would qualify as a near‐to‐equilibrium system. It embodies a motion perpendicular to the plane of the membrane for the pumping of protons. The mechanism is both cooperative and synchronized. Each transport event results in a compaction of the protein across the membrane provoking a neighboring pump to expand and visa versa. The mechanism implies that pumps be dimers or multimers in living membranes although they could pump individually in reconstituted in bilayers. It is the nature of the pumping mechanism that it can be restarted with Brownian motion if it falters.
Separate Regions of Glucocorticoid Receptor, Coactivator TIF2, and Comodulator STAMP Modify Different Parameters of GR‐mediated Gene Induction
Authors: Awasthi Smita , Simons S. Stoney 
Published: June 2021

Coregulators, such as TIF2, and comodulators, such as STAMP, modify several aspects of glucocorticoid receptor (GR)‐mediated gene induction. Varying the levels of these factors alters not only the total level of transactivation (Amax) but also both the position of the dose‐response curve (e.g., EC50) for agonists and the amount of partial agonistic activity of antagonists (as a percent of full agonist activity under the same conditions). Our lab has found that TIF2 and STAMP appear to form a complex with GR that results in more than additive changes in Amax, EC50, and percent partial agonist activity for GR‐inducible genes. Using gene activation, mammalian two‐hybrid, and co‐immunoprecipitation (co‐IP) assays with truncated proteins; we find that selected regions of each protein (GR, TIF2, and STAMP) are required in the ternary complex to modify some, but not all, induction properties. Modulation of EC50 requires the most domains of each protein. Smaller fragments are sufficient to modify the Amax and/or percent partial agonist activity. Even less is required to form a complex. The data suggest that the pathways controlling Amax, EC50, and percent partial agonist activity of GR transactivation are physically separable and may utilize different transcriptional cofactors. Thus, greater physiological control of glucocorticoid action may be possible via agents that modify individual induction parameters.Source of research support: NIH Intramural Program