bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrin‐Mediated Adhesion and Signaling in the Neurovascular Niche
Authors: McCarty Joseph Henderson , Mobley Aaron Kyle , Tchaicha Jeremy Hatem , Hossain Mohammad Golber , Shin Jae‐kyung , Jung Youngsin
Published: June 2021

Neural progenitors (NPs) in the central nervous system (CNS) reside in a neurovascular niche. Cell‐cell and cell‐extracellular matrix interactions within the neurovascular niche regulate NP self‐renewal and differentiation; however, the mechanisms used by NPs to communicate with blood vessels remain largely uncharacterized. We have shown previously that genetic ablation of αvβ8 integrin expression in NPs leads to profound neurovascular phenotypes due to defective cell‐ECM adhesion in the neurovascular niche. Here, we have analyzed αvβ8 integrin in NPs purified from wild type or αv and β8 integrin knockout (KO) mice. Cells lacking αvβ8 integrin display reduced self‐renewal, as assayed by neurosphere formation. Furthermore, αvβ8 KO cells display preferential differentiation toward the astroglial lineage following serum exposure. Subventricular zone NPs in adult β8 integrin KO mice show reduced self‐renewal, which is associated with abnormal SVZ ultrastructure. KO mice also develop size‐reduced olfactory bulbs, indicative of impaired NP growth and differentiation. Our various data for αvβ8 integrin are very similar to results for a regulator of NP self‐renewal, Bmi1. Indeed, our data mining efforts reveal that Bmi1 regulates αvβ8 integrin gene expression. Collectively, these studies identify essential roles for αvβ8 integrin in NP self‐renewal and differentiation in the CNS neurovascular niche.
CD36 Modulates Macrophage Spreading and Migration in response to oxidized LDL
Authors: Park Young Mi , Febbraio Maria , Silverstein Roy L.
Published: June 2021

CD36, a class B scavenger receptor expressed on macrophages has been implicated in many biological processes including atherosclerosis. Previous work showed that CD36 mediates uptake of oxidized LDL (oxLDL) and transmits intracellular signals. We hypothesized that oxLDL may affect macrophage adhesion and migration by modulating cytoskeletal function. OxLDL, but not native LDL, inhibited LPS induced efflux of peritoneal macrophages in vivo and MCP‐1 directed macrophage migration in a modified Boyden chamber assay. OxLDL induced rapid spreading on serum‐coated glass, and actin polymerizaton. Western blots of extracts from macrophages incubated with oxLDL showed sustained phosphorylation of focal adhesion kinase (FAK) and dephosphorylation of src homology 2‐containing phosphotyrosine phosphatase, SHP‐2; this was associated with oxidative modification of cysteine residues. These responses were significantly blunted in macrophages from CD36 null mice. OxLDL induced ROS generation in a CD36‐dependent manner, which may provide a mechanism for SHP‐2 modification. Macrophage migration could be restored using antioxidants and NADPH oxidase inhibitors. We conclude that CD36 signaling in response to oxLDL contributes to cytoskeletal rearrangement and modulates macrophage spreading and migration. This may induce trapping of macrophages in the arterial intima and thus promote atherosclerosis.
Association of Hypoxia with Impaired Remodeling Mechanisms in the Abdominal Aortic Aneurysm (AAA) Wall
Authors: Chew Douglas W. , Sakamoto Naoya , Sakamoto Makiko , Sanders Lori B. , Makaroun Michel S. , Vorp David A.
Published: June 2021

AAA rupture occurs when wall stresses exceed the wall strength. We tested two hypotheses: 1) the AAA wall near thick intraluminal thrombus (ILT) exhibits impaired remodeling compared to wall near thin ILT and 2) macrophages (mΦ) cultured under hypoxic conditions exhibit altered enzyme expression compared to mΦ in normoxic conditions. For 1, pairs of AAA wall, selected based on disparate thicknesses of near ILT, were snap frozen. QPCR was used to compare the gene expression. Total wall thickness was measured on H&E sections. For 2, peripheral mononuclear cells were isolated from human buffy coats and cultured under hypoxic (2% O2) or normoxic (20% O2) conditions in serum‐free medium. Media levels of MMP‐9 were determined using ELISA. We found a down‐regulation of MMP‐2, MMP‐9, uPA, tPA, CD68, and collagen IV, and an up‐regulation of HO‐1, ORP‐150, ICAM‐1, IL‐12, IFN‐γ, and iNOS in AAA wall near thick ILT compared to AAA wall near thin ILT. AAA wall thickness was positively correlated (ρ=0.476) to ILT thickness. MΦ cultured in hypoxic conditions showed a marked decrease in secreted MMP‐9 activity and protein levels relative to mΦ cultured in normoxic conditions on collagen I or fibrin. The results support hypothesis 1, suggesting that compared to AAA wall near thin ILT, the AAA wall adjacent to a thick ILT has a more activated immune component and impaired remodeling mechanisms. Our results also suggest that the hypoxic environment of the AAA wall may lead to an alteration in protein expression by mΦ. This work was supported by NIH R01‐HL79313.
Sall genes regulates limb patterning through modulation of region‐specific Hox activities in mice
Authors: Kawakami Yasuhiko , Nishinakamura Ryuichi , Belmonte Juan Carlos Izpisua
Published: June 2021

Sall genes encode zinc finger transcription factors, and Sall1 and Sall4 are causative genes for human syndromes, such as Towns‐Brocks syndrome and Okihiro syndromes, respectively. Patients with these syndromes show multiple defects including those in limbs. In order to understand the molecular mechanisms by which Sall genes control limb development, we have analyzed mice with targeted mutations in Sall1 and Sall3. While a single knockout of Sall1 and Sall3 shows subtle defects, double mutants exhibited severe defects in autopod development. We found that Sall1 interacts with Hoxa13 and Hoxd13, important genes controlling proper development of the autopod. Further analyses suggest that the coordinated action of Sall and Hox regulates target gene expression and patterning of the autopod. Our study provides molecular insights into how region‐specific morphogenesis is regulated in the autopod.

Supported by NIH (5 R01 HD034538‐10) and Grant‐in‐aid by the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Real‐Time Anatomical Visualization: Digitizing the Human Gait
Authors: Pollo Fabian E.
Published: June 2021

Gait analysis can be described as the systematic study of human walking using visual observation augmented by instrumentation for quantifying body movements. Three dimensional motion capture systems typically consist of 5 or more cameras which record passive or active markers that are strategically placed on the subject's body. The three‐dimensional position of each marker is calculated in space and then utilizing special algorithms the position, velocity and acceleration can be determined for any segment. Animation by way of these motion capture systems has revolutionized the video gaming industry and animated movie creation. In addition, animation is finding its way into research and medicine investigating pathologies and interventions that affect the locomotor system. Being able to visually portray the motion through three dimensional animation allows for more meaningful interpretation of conditions being studied. Technology has progressed to the point where animation is possible in real‐time which allows for instant feedback for both the examiner and examinee. This instant feedback is showing promise in helping individuals with walking abnormalities in which gait training is necessitated.
Using Modified Team‐Based Learning in the Medical Histology Lab
Authors: MacPherson Brian R , Brueckner Jennifer K
Published: June 2021

Converting the medical histology laboratory experience to a digital format left us with the responsibility of ensuring the students still knew how to use a microscope for future courses in the curriculum. Weekly modified team‐based learning (TBL) sessions involving use of the mucoscope were incorporated to facilitate this. Each TBL session utilized the typical IRAT where students individually accessed the 5 question quiz on the selected organ system. There was a 48 hour window in which they were expected to do this. On the morning of the GRAT (termed the Laboratory Analysis Exercise or LAE) the case was downloaded by the students in the lab. Each case routinely either referenced a pathological slide in their box, or provided an image and asked them to examine a slide of the organ in its normal state. The diagnosis was provided and the students were asked to complete 5 questions about the case ‐ as a group ‐ and submit their group answers by email within a specified time‐frame. Questions involved asking them to describe what they observed as being different structurally about the pathological specimen; related structure to function; and also related their tissue‐level studies to their ongoing gross anatomy experience. This presentation will provide a typical case; outline the benefits and issues as seen by the students in their course evaluation as well as the student liaison group; and lastly the benefits observed by the faculty.
An anatomical backbone for an integrated first‐year medical curriculum
Authors: Klement Brenda J , Paulsen Douglas F , Wineski Lawrence E
Published: June 2021

One current trend in medical education is weaving basic science course content into an integrated curriculum. Related challenges to traditional curricula with separate, department‐based, courses include: curricular governance, examination logistics, lecture and laboratory scheduling, and content distribution among faculty. Having already integrated our anatomy curriculum into a single Human Morphology course with regional dissection at its core, our course recently became the backbone for integrating our entire first‐year medical curriculum. Existing lectures from all courses were rearranged and aligned by topic and supplemented with clinical correlations. Reshuffling and shortening the lectures reduced unnecessary redundancy, reduced hours in class, and reinforced learning by juxtaposing content coverage from multiple perspectives. The logistics of curriculum scheduling, management, and delivery developed over one year in meetings among course directors and other key faculty. The initial outcome maintains course autonomy and course directors. Cross‐departmental faculty meetings continue to provide unprecedented interdepartmental faculty communication regarding teaching, learning, and content. We expect the curriculum to continue evolving toward full integration, retaining full regional dissection as a core element. Supported in part by NIH P03 1B040107 and G12‐RR03034.
Nonhuman primate models to study chemokine mechanisms for eosinophil trafficking
Authors: Miller Lisa Ann
Published: June 2021

Exposure to air pollutants during early life may contribute to the pathogenesis of allergic airways disease. Using an infant rhesus monkey model, we have reported that chronic inhalation of house dust mite (HDM) can result in airway eosinophilia in association with increased eotaxin‐3 expression. In this study, we have determined the effects of episodic ozone exposure on HDM‐induced airway eosinophilia and esoinophilic chemokine expression in 3 month old infant monkeys. In response to HDM and/or ozone, airway eosinophils were significantly increased in lavage samples. In contrast, the volume of airway tissue eosinophils increased only in animals treated with house dust mite alone. Eotaxin‐3 expression correlated with eosinophil volume in airway tissue, but not lavage. A significant increase in eotaxin‐2 protein and gene expression was observed with combined HDM+ozone exposure that did not correlate with the presence of eosinophils. These findings provide further support for the role of eotaxin‐3 as a prevalent chemokine mediator of eosinophil trafficking in the lung, and suggest that oxidative stress alters the eosinophilic chemokine profile of airways during postnatal development.
CD4 T cell‐mediated neuroprotection: Relevence to ALS and Motoneuron Injury
Authors: Jones Kathryn
Published: June 2021

We have identified a beneficial role for the peripheral immune system in motoneuron reparative processes through use of the mouse facial motoneuron (FMN) injury paradigm, which involves a peripheral nerve injury outside the blood‐brain‐barrier, in conjunction with immunodeficient mouse models (including the recombinase‐activating gene‐2 knockout (RAG‐2KO) mouse which lacks functional T and B cells; Serpe et al., 1999). We initially focused on understanding the mechanism by which the immune system FMN survival following injury. Accomplishments thus far include the identification of the CD4+ effector Th2 cell as the critical cell needed for FMN rescue from axotomy‐induced cell death through an antigen‐specific process requiring peripheral activation followed by central re‐activation and brain‐derived neurotrophic factor (BDNF) as the molecule required for Th2 cell‐mediated FMN rescue. Although the CD4+ effector Th1 cell is not required for FMN rescue, lymph node analysis indicates that both a Th1 and Th2 cytokine profile develops in response to peripheral nerve injury. We also have determined that functional recovery from facial paralysis induced by facial nerve crush injury is significantly impaired in immunodeficient animals, but is restored to wild‐type (WT) after reconstitution of the immune system. Collectively, these findings provide the foundation for a working model of CD4+T cell‐mediated motoneuron survival and axonal regeneration after injury. Key to this model is the new concept that CD4+ effector T cell subsets play distinctive roles in motoneuron reparative processes, with the Th2 cell mediating FMN survival through a central BDNF‐dependent process and the Th1 cell mediating functional recovery through participation in the lesion site pro‐inflammatory response. How this concept may be applied to the disease process of ALS, a fatal motoneuron disease, will be discussed.
Feasting, Fasting and Fermenting: Glucose sensing in yeasts
Authors: Johnston Mark
Published: June 2021

Glucose fuels life. Most cells prefer it as a food source, and have sophisticated mechanisms for sensing it for efficient use. Yeast and tumor cells metabolize glucose in a seemingly foolish way: they eschew its oxidation (forgoing up to 38 ATPs), and choose to ferment it (settling for 2 ATPs). Yeast cells must sense glucose to know when they must utilize it efficiently because levels are low, and when it is plentiful and can be wasted in fermentation. Yeast throttles glucose utilization at the rate‐limiting step: transport. We discovered a novel glucose sensing system that adjusts this throttle by deploying the appropriate glucose transporters through regulation of their HXT genes. This pathway begins with glucose sensors in the membrane (Snf3 and Rgt2), founding members of a novel class of nutrient receptor related to nutrient transporters. The sensors are coupled to a casein kinase I (Yck), that transduces the glucose signal to a transcriptional repressor (Rgt1) of HXT genes, and its regulators (Mth1 and Std1). The fateful step in the pathway is glucose‐induced degradation of Mth1 and Std1, which relieves repression of HXT genes. This glucose sensing pathway enables yeasts’ profligate lifestyle by ensuring efficient glucose transport.
Lipids and Membrane Proteins that Regulate Genes of Lipid Metabolism
Authors: Jump Donald B. , Wang Yun
Published: June 2021

The liver plays a central role in whole body lipid metabolism and responds rapidly to changes in dietary fat composition. Fatty acid effects on hepatic lipid metabolism are mediated, at least in part, through three transcriptional regulatory networks: PPARα, SREBP1 and ChREBP/MLX. Changes in PPARα activity and expression of its target genes correlate well with changes in intracellular non‐esterified fatty acids. Ligand activation studies, however, suggest that fatty acid structure affects PPARα activity. One metabolic pathway was identified as potentially affecting PPARα activity, i.e., fatty acid elongation. Fatty acid elongases are ER‐associated enzymes. An adenoviral‐mediated approach was used to over express the fatty acid elongase, Elovl5, in mouse liver. Elevated Elovl5 enzyme activity promoted changes in both hepatic and blood lipid composition. Elevated Elovl5 activity also attenuated expression of several PPARα‐regulated genes without significant effects on SREBP1‐ or ChREBP/MLX‐regulated genes. Amongst the 4 elongase subtypes expressed in liver, Elovl5 is abundant and well‐regulated. These studies suggest that metabolic pathways affecting fatty acid structure may play a role in controlling PPARα function. Supported by NIH DK43220.
Dynamic regulation of histone methylation by demethylases
Authors: Shi Yang
Published: June 2021

Recent studies identified many histone demethylases indicating a centrol role these enzymes play in histone methylation dynamics. I will discuss our continued efforts in the identification of new histone demethylases and studies of their roles in development and human diseases.
Structure and function of human telomerase and H/ACA RNA
Authors: Feigon Juli
Published: June 2021

The telomere ends of linear chromosomes are replicated by the riboprotein complex telomerase. Telomerase is a large riboprotein complex that uses an integral RNA template and a specialized reverse transcriptase to processively synthesize the G‐rich strand. Telomerase has only a low or undetectable level of activity in normal somatic cells, but is highly active in most cancers, and is thus of interest as a target for anticancer drugs. The RNA component of telomerase plays an integral role in catalysis, localization, and processing. Results on the structure of domains of the RNA component of human telomerase, and how mutations in the RNA affect the structure and function of telomerase, will be presented. These domains include a pseudoknot containing a catalytically essential triple helical region and an H/ACA domain. Related results on H/ACA snoRNAs involved in pseudouridylation will be presented.
Randomized controlled trial of vitamin B12 supplementation in Mexican women with a high prevalence of B12 deficiency; predictors of biochemical and hematological response
Authors: Shahab‐Ferdows Setareh , Anaya Miriam Aracely , Rosado Jorge Louis , Pogribny Igor , Allen Lindsay H.
Published: June 2021

Low serum B12 (sB12) is prevalent in Latin America. This randomized controlled trial assessed functional significance of low sB12 from response to supplementation of women aged 18–59 in rural Querétaro. Subjects were assigned to B12 (1 dose 1 mg i.m. + 500 ug/d oral, 3 mo, n=70) or placebo (n=62). Measures at baseline and 3 mo were CBC; sB12, holotranscobalamin (TC), folate, MMA; tHcy; DNA methylation, bone alkaline phosphatase (BAP). At baseline 10% were B12 deficient (sB12 <150 pmol/L) and 21% marginal (150–220 pmol/L). TC was low (<35 pmol/L) in 22% and correlated with sB12 (r=0.7, P<0.001). MMA >270 nmol/L and tHcy>12μmol/L occurred in 17% and 35%, and correlated with sB12 (r= −0.28, P<0.0007, and r=−0.20, P<0.01) indicating functional deficiency. Supplementation sig. increased sB12 by 384 pmol/L and holoTC by 80 pmol/L, lowered MMA by 55 nmol/L and tHcy by 1.3 μmol/L, but had no sig. effect on hematology, BAP or DNA. Defining responders to B12 as above the placebo group's regression line for sB12 and TC or below for MMA and tHcy, 79% responded in sB12, 70% TC, 17% MMA, 15% tHcy, 46% in sB12 + TC, but only 1% in all 4 measures. Greater response in SB12 was predicted by higher baseline tHcy and lower gastrin; in TC by younger age and lower gastrin; BAP by higher MMA; tHcy by no baseline variable. Functional B12 deficiency was confirmed but variable response of B12 status markers complicates evaluation of intervention efficacy. UCMexus & USDA.
Protective effects of green tea in suppressing autoimmune response in Type 1 Diabetes
Authors: Wong Carmen P , Elias Valerie , Ho Emily , Bray Tammy
Published: June 2021

Autoimmune disease onset and progression involves both genetic and environmental factors. Dietary factors are modifiable environmental factors that affect the outcome of autoimmune diseases. Populations that consume green tea (GT) have one of the lowest T1D disease incidence, thus GT potentially can prevent/blunt autoimmune responses. However, how GT modulates immune functions and suppress autoimmunity is unclear. Type 1 diabetes (T1D) is a model for studying the effects of GT on autoimmune diseases. We hypothesize that GT suppress T1D autoimmune response by restoring immune regulation. We characterized the effects of GT on T1D using nonobese diabetic (NOD) mice which develop spontaneous T1D. NOD mice were provided with 2% GT or water. After 5 wks, we examined the extent of insulitis in the pancreas. GT‐treated NOD mice had significant reduced insulitis compared to control. We hypothesize that GT suppressed insulitis by directly affecting regulatory T cells (Treg) and dendritic cells (DC), both critical in controlling autoimmunity. Indeed, GT‐treated NOD mice had 1) increased Treg frequency, 2) decreased DC TNFalpha production, and 3) reduced T cell proliferation and IFNgamma production. Our data suggest GT has potent immunomodulatory effects on multiple cell types in vivo, and provides the foundation for understanding the mechanisms by which GT modulate autoimmune response and immune function in general.
Effects of Active Hexose Correlated Compound (AHCC) on humoral immunity in food deprived mice immunized with ovalbumin (OVA)
Authors: Aviles Hernan O , O'Donnell Phyllis , Orshal Julia , Sen Dwaipayan , Fujii Hajime , Sonnefeld Gerald
Published: June 2021

Adequate nutrition and a functional immune system are essential to resist infections. Previous studies have shown that AHCC, a natural compound, enhances survival compared to controls of food‐deprived mice exposed to bacterial infection. The mechanisms of AHCC effects on the immune system remain unclear. The objective of this study was to evaluate the humoral immune response of food deprived mice after immunization with OVA. Food‐deprived mice receiving either AHCC or excipient were immunized with OVA. Ten days after immunizations, blood and spleen cells were obtained under sterile conditions. Differential cell counts were performed on whole blood and specific anti‐OVA antibody levels (IgM, IgG, IgG1, IgG2a, IgG2b, and IgG3) were measured in plasma. Lymphocyte phenotypes (CD3+, CD8+, CD4+, CD19+, NK+, Gr1+) were assessed by flow cytometry. Spleen function was evaluated by determining cell proliferation in response to mitogens (lipopolysaccharide [LPS], OVA and LPS+OVA) and B cell function by ELISpot (IgG and IgM). The results indicate that AHCC treatment induced a significant increase in the number of circulating leukocytes and an increase in the percentage of CD4+ T helper lymphocytes. AHCC treatment also induced an increased antibody response against OVA, especially of the IgG3 type as well as an increased proliferative response to stimulation with LPS and OVA antigens. Taken together, these results suggest that AHCC‐treatment can compensate for the detrimental effects of food deprivation on humoral immunity. Additional studies using vaccines that require the development of a strong humoral response are necessary to fully understand the potential of AHCC to be used as an adjuvant.
Promotion of bone growth by dietary soy protein isolate: Comparison with dietary casein, whey hydrolysate and rice protein isolate in growing female rats
Authors: Chen Jin‐Ran , Singhal Rohit , Lazarenko Oxana P , Badger Thomas M. , Ronis Martin J. J.
Published: June 2021

The effects of different dietary protein sources: casein (CAS), soy protein isolate (SPI), whey protein hydrolysate (WPH) and rice protein isolate (RPI) on bone were studied in intact growing female rats and in ovarectomized (OVX) rats showing sex steroid deficiency‐induced bone loss. In addition, SPI effects on bone were compared to those of 17β‐estradiol (E2) in the OVX osteopenic rat models. Peripheral quantitative computerized tomography of tibia demonstrated that SPI, WPH and RPI diets all had positive effects on either bone mineral density or content (BMD, BMC) relative to CAS, but SPI had the greatest effects in both intact and OVX female rats. Soy and E2 showed positive effects on BMD and BMC in OVX rats, respectively, but trabecular BMD was lower in SPI+E2 groups compared to E2 alone. E2 reduced both serum bone formation (osteocalcin, alkaline phosphotase) and resorption (RatLaps) markers. In contrast, SPI increased serum bone formation markers but suppressed bone resorption markers. Interestingly, both SPI and E2 increased alkaline phosphatase gene expression while SPI but not E2 decreased RANKL and estrogen receptor gene expression in RNA isolated from whole tibial bone. These data suggest that dietary protein source can affect bone quality and that beneficial SPI effects on bone are modulated by E2 status. Supported in part by ARS CRIS #6251‐51000‐005‐03S.
Decreased hephaestin expression and activity leads to decreased iron efflux from differentiated Caco2 cells
Authors: Vulpe Chris , Attieh Zouhair K , Chen Huijun
Published: June 2021

Iron is transported across intestinal brush border cells into the circulation in at least two distinct steps. Iron can enter the enterocyte via the apical surface through several paths. However, iron egress from the basolateral side of enterocytes converges on a single export pathway requiring the iron transporter, ferroportin, and hephaestin, a ferroxidase. Copper deprivation leads to reduced hephaestin protein expression and activity in mouse enterocytes and intestinal cell lines. We tested the effect of copper deprivation in differentiated Caco2 cells grown in transwells and found decreased hephaestin protein expression and activity. Furthermore, this decrease correlates with a decrease of 55Fe release from the basolateral side of Caco2 cells. Presence of ceruloplasmin, apo‐transferrin or holo‐transferrin did not significantly alter the results observed. Repletion of copper in Caco2 cells leads to reconstitution of Hephaestin protein expression, activity and transepithelial iron transport.
EFFECT OF PRENATAL DHA SUPPLEMENTS ON INFANT MORBIDITY IN A DOUBLE‐BLIND RANDOMIZED CONTROLLED TRIAL IN MEXICO
Authors: Imhoff‐Kunsch Beth Christen , Stein Aryeh , Martorell Reynaldo , Parra‐Cabrera Socorro , Rivera Juan , Ramakrishnan Usha
Published: June 2021

In a double‐blind randomized controlled trial conducted in Mexico, pregnant women were supplemented daily with 400mg docosahexaenoic acid (DHA) or placebo from 18â22 wk gestation through delivery. To evaluate whether in utero exposure to DHA, which has been shown to modulate immune function, influences infant morbidity, we assessed illness symptoms at 1, 3 and 6 mo. Caregivers reported symptoms such as fever, cough and rash in a 15 d recall administered at each study visit. Baseline maternal characteristics for the 851 infants with morbidity data were comparable between groups. Although the prevalence of symptoms did not differ between groups at 1, 3, and 6 mo, duration varied; 10, 22, and 33% of infants had cough with a mean duration of 0.5, 1.2 and 2.2 d at 1, 3 and 6 mo, respectively. At 1 month, Group I (GI) experienced 48, 33, 19 and 79% increased risk (P<.01) of being ill for more days with cough, phlegm, nasal congestion and nasal secretion, respectively, but had a reduced risk of longer duration of vomiting and rash. At 3 mo, GI had a higher risk of experiencing more days with cough, wheezing and rash (RR: 1.19, 1.74, 1.57; P<.05). GI experienced a reduced risk of more days with cough, phlegm, wheezing and vomiting (RR: .86, .83, .70, .39; P<.001) but a higher risk of difficulty breathing (RR: 2.32) at 6 mo. The potential influence of DHA on illness duration will be clarified upon un‐blinding the data in March 2008.
Metabolic Syndrome in Elderly Living in Marginal Peri‐Urban Communities in Quito, Ecuador
Authors: Sempértegui Fernando , Estrella Bertha , Tucker Katherine L , Hamer Davidson H , Narvaez Ximena , Sempértegui Mercy , Rodríguez Alicia , Noel Sabrina , Dallal Gerard D , Selhub Jacob , Meydani Simin N
Published: June 2021

The number of the elderly in Latin America is expected to double in the next few decades. Metabolic syndrome (MetS) is associated with high morbidity and mortality. However, little is known about MetS in Latin America. The objective of this study was to examine the prevalence of MetS in a low income urban area, and to evaluate the association between blood micronutrient, homocysteine (tHcy) and CRP levels with MetS. We performed a cross‐sectional study of 352 elderly (≥ 65 years) Ecuadorians living in a peri‐urban slum community in Quito, Ecuador. MetS was prevalent (45%)—more so among women (53%) than men (29%). In addition, many of those without MetS exhibited one or more risk factors for MetS. Plasma micronutrient deficiencies were prevalent: >70% for vitamin C, >45% for Zinc, and >20% for vitamin B12 and folate. Vitamin C and E concentrations were inversely, and CRP positively associated with MetS. The co‐existence of MetS with micronutrient deficiencies indicates that elderly Ecuadorians suffer from the double burden of diseases associated with the nutrition transition in less‐developed countries. Research is needed to determine causal factors, but interventions to normalize blood lipids, reduce hypertension and weight gain, and to improve micronutrient status, appear to be needed in this population. Supported by NIH Fogarty International Center (1 R03 TW005779‐01A1), NIA (2R01 AG009140‐10A1), and USDA (Contract #58‐1950‐7‐707).
Receptor‐dependent lycopene uptake in vivo: studies in scavenger receptor null mice
Authors: Zarkhin Eli , Zaripheh Susan , Gong Xiaoming , Xiao Fan , Febbraio Maria , Rubin Lewis P
Published: June 2021

Cellular uptake of various carotenoids is not well understood. Recent investigations indicate that the Class B “scavenger receptor” SR‐B1 may govern cellular uptake of b‐carotene, lutein and vitamin E. To determine whether other lipoprotein (scavenger) receptors participate in carotenoid uptake in vivo, we examined mouse strains in which the genes for specific receptors (LDL Receptor [LDLR], SR‐A, CD36) were deleted by homologous recombination. METHODS: Male mice were housed in metabolic cages and fed lycopene‐enriched (0.25 g/kg chow) or standard diets for 30 days. Four genotypes (n=12 per group) were studied: wild type, LDLR−/−, SR‐A−/− and CD36−/−. Food intake and body weight were recorded every second day. After the feeding period, plasma and tissue samples collected. Sample extracts were prepared and lycopene measured by HPLC‐UV was normalized to protein content. RESULTS: Liver lycopene accumulation (ng lycopene/g tissue) was significantly reduced in SR‐A−/−, LDLR−/− and CD36−/− mice by 85%, 67% and ~30%, respectively, compared to wild type (p<0.001). Plasma lycopene concentrations were decreased by ~50% in SR‐A−/− mice (p<0.001) but were increased by 180% in LDLR−/− mice (p<0.001). CD36−/− plasma lycopene did not significantly differ from that of wild type. Prostate gland lycopene uptake profiles were similar to the plasma lycopene results. CONCLUSIONS: In addition to SR‐B, several scavenger receptors (SR‐A, CD36 and LDLR), particularly SR‐A, are important mediators of tissue‐specific lycopene uptake in the mouse. These findings are potentially important for dietary enrichment strategies and treatment of disorders, e.g., atherosclerosis and carcinogenesis, where enhancing carotenoid uptake may reduce risk. (NIH HD42174, RR18728)
Green tea (GT) extract lowers the lymphatic absorption of benzo[a]pyrene (BaP) in rats
Authors: Noh Sang K. , Kim Juyeon , Seo Yunjung , Koo Sung I.
Published: June 2021

Recently, we have shown that GT extract (GTE) or its catechins markedly lower the intestinal absorption of cholesterol and fat in rats. BaP is a lipophilic organic pollutant. The present study was conducted to examine the effect of enteral infusion of GTE on the lymphatic absorption of BaP in rats. Adult male rats with lymph cannulae were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion containing 1.0 mg BaP labeled with 14C (14C‐BaP), 452 μmol triolein (oleic acid, OA), 20.7 μmol cholesterol, and 3.1 μmol α‐tocopherol (αTP), and 396.0 μmol Na‐taurocholate without (control) or with 76.0 mg GTE in PBS buffer (pH, 6.4). Lymph was collected hourly for 8 h. No significant difference was noted in lymph flow (14.5 ± 2.9 mL/8 h in GTE vs. 15.0 ± 1.8 mL in control). However, the infusion of GTE markedly lowered the lymphatic absorption of 14C‐BaP (7.6 ± 3.2% dose/8 h) compared with controls infused with the lipid emulsion alone (14.4 ± 2.7%). The results indicate that GTE has a profound inhibitory effect on the intestinal absorption of BaP in rats. The mechanism(s) by which GTE reduces BaP absorption remains to be determined. A study is currently underway examining whether GTE would affect the biliary secretion of BaP in rats.

Supported by the Korea Research Foundation Grant funded by Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF‐2006‐003‐C00312)
Food group consumption patterns in a sample of predominantly low‐income children
Authors: Kranz Sibylle , Mitchell Diane , Kumanyika Shiriki K. , Stettler Nicolas
Published: June 2021

This study analyzed dietary and anthropometric data of 2–11 years olds at five community health centers (CHC) from medically underserved areas of in the U.S. Northeast. Children provided two (n = 24) or three days (n = 190) of 24‐hour recalls. Half of the children were males; half were 2–5 years old; 70% were low‐income; and 64% were at risk for overweight or overweight. Intake reports were disaggregated and average daily intake of total energy (kcal) and MyPyramid food groups (fruit, vegetable, grain, dairy, and meat/meat alternatives in cups or ounces) calculated. Approximately 9% of the sample met all food group recommendations while 6% met none. Half of the sample met the intake recommendation for grains. More preschoolers than 6–11 year olds met the remaining food groups (36% vs. 23% for vegetables, 64% vs. 45% for fruits, 72% vs. 55% for meat, and 55% vs. 49% for dairy). Sixty‐three percent of the children had energy intakes >110% the age‐and gender‐specific Estimated Energy Requirements. In this sample, 73% of the children meeting at least four out of the five recommendations had healthy body weight. Thus, younger children were more likely to meet the intake recommendations and meeting food group recommendations was associated with healthy body weight.

This study was supported by a seed grant from the Children, Youth, and Family Consortium at the Pennsylvania State University.
Dietary patterns related to fat and bone mass in preschoolers
Authors: Wosje Karen S. , Khoury Philip R. , Copeland Kristen A. , Daniels Stephen R.
Published: June 2021

We aimed to determine dietary patterns (DP) related to both fat (FM) and bone mass (BMC) in preschoolers. FM and BMC were measured by DXA (Hologic QDR4500) at age 4 y (n = 326). Four 3‐d diet records collected from age 3 to 4 y were used to estimate intake (servings/d) of 34 food groups (NDS v 2005). We used reduced rank regression to extract DP to explain a maximum variation in FM and BMC simultaneously. The 1st DP (DP1) was associated with both higher FM and higher BMC, explaining 14% (FM) and 13% (BMC) of variation. DP2 was associated with lower FM and higher BMC, explaining an additional 4% of variation in each. DP1 was characterized by high intake of non‐whole grain, fried food, lunch meat, egg, dessert and discretionary fat. DP2 was characterized by high intake of whole grain, vegetables, lunch meat, beans, soy and savory snacks. DP1 (r = 0.6) and DP2 (r = 0.4) scores were related to kcal intake (p < 0.01). In ANCOVA models adjusting for activity, age, sex, BMI, and ht, DP1 scores, but not kcal intake, were associated with FM and BMC (p ≤ 0.01). Using the residuals of the relation between kcal and DP1 scores in place of DP1 scores, both the residuals and kcal were associated with FM (p < 0.05); and residuals but not kcal were associated with BMC (p < 0.01). DP2 scores and residuals persisted in adjusted models for FM. A diet proportionately high in fat, with a high absolute amount of protein, is related to both high adiposity and high BMC in preschoolers. NIH R21DK077100
Soluble CD44 secretion promotes the expression of an aggressive tumor phenotype in human colon cancer
Authors: Jothy Serge , Gardner Helena , Subramaniam Venkateswaran
Published: June 2021

CD44, a widely distributed cell surface glycoprotein and a receptor for hyaluronan (HA) has been implicated in facilitating tumor growth and metastasis, antiapoptosis and directional motility of cancer cells. CD44 shedding has been observed in different tumor cell types but not using cell lines derived from colorectal cancer. In order to investigate the role of soluble CD44 (CD44 sol) in colon cancer cell growth, SW620, a human colon cancer cell line deficient in CD44 standard isoform expression was stably transfected with human CD44 cDNA containing exons 1–5, 15 and 16 of the human CD44. Western blot analyses demonstrated the presence of 78 kDa soluble CD44 protein in the culture supernatant of stably transfected cell lines as compared to control cells transfected with the empty vector control. These CD44 sol transfected cells showed higher cell proliferation and clonal growth in vitro, confirmed by MTT and clonogenic assays respectively, when compared to control cells. Cell adhesion to HA was significantly lower with CD44 sol clones compared to control cells. Western blot analyses for cleaved PARP were negative in lysates from CD44 sol cells suggesting resistance to apoptosis. These findings indicate that the secretion of soluble CD44 contributes to colon cancer growth, possibly as a decoy receptor.
P120‐Catenin controls junctional leukocyte transmigration in vitro by regulating VE‐Cadherin surface expression
Authors: Alcaide Pilar , Newton Gail , Sehrawat Seema , Mayadas Tanya N , Vincent Peter , Kowalczyk Andrew P , Luscinskas Francis W
Published: June 2021

Vascular Endothelial‐Cadherin (VE‐Cad) is localized to adherens junctions at endothelial cell borders and forms a complex with α‐, β‐, γ‐, and p120‐catenins (p120). We previously showed that this complex disassociates to form short‐lived “gaps” during leukocyte transendothelial migration (TEM), but whether these are required for leukocyte passage through the endothelium is not clear. p120 has been shown to control VE‐Cad surface expression by endocytosis. We hypothesized that p120 regulation of VE‐Cad surface expression would have functional consequences for leukocyte TEM. Here we show that endothelial cells transduced with an adenovirus expressing a p120GFP fusion protein significantly increased VE‐Cad expression at the cell surface in association with decreased VE‐Cad phosphorylation. High p120GFP expression prevented VE‐Cad gap formation and neutrophil TEM in human umbilical vein or dermal microvascular endothelial cells; if TEM occurred, the length of time required was prolonged. We found no evidence that VE‐Cad endocytosis plays a role in VE‐Cad gap formation and show that this process is regulated by changes in VE‐Cad phosphorylation. In fact, a non‐phosphorylatable VE‐Cad mutant prevents TEM. Our data provide compelling evidence that VE‐Cad gap formation is required for leukocyte TEM and identify p120 as a critical intracellular mediator of this process. Supported by NIH HL36028.
Endothelial‐derived microparticles inhibit pulmonary artery vasodilation
Authors: Peterson Danielle B. , Kaul Sushma , Wang Jingli , Jones Deron W. , Oldham Keith T. , Pritchard Kirkwood A. , Sander Tara
Published: June 2021

Endothelial‐derived microparticles (EMPs) are produced by endothelial cells in response to cell injury, activation and apoptosis. Elevated plasma concentrations of EMPs are associated with a variety of vascular and inflammatory diseases, including acute lung injury (ALI). However, the mechanisms by which EMPs contribute to pulmonary disease are unclear. We hypothesize that EMPs contribute to ALI by inhibiting endothelium‐mediated vasodilation in the pulmonary vasculature. To test this hypothesis, acetylcholine (ACh)‐mediated vasodilation was quantified using isolated thoracic aorta (TA) and pulmonary artery (PA) rings of C57BL/6 mice in the presence or absence of EMPs (20 K or 100 K EMPs/ml). Concentration dependent inhibition of ACh‐mediated vasodilation was observed for both TA and PA rings; furthermore, PA rings are more sensitive to the inhibitory effects of EMPs. In conclusion, EMPs attenuate endothelium‐mediated vasodilation at pathophysiologically relevant concentrations. EMPs also act in a tissue specific manner affecting the pulmonary vasculature disproportionate to other vascular beds. These data suggest that EMP damage to pulmonary endothelial cells may contribute to ALI. Funding provided by the Children's Research Institute and MCW Department of Surgery.
Food Insecurity and Food Environments of Low‐income Older Adults in Northeast Georgia
Authors: Lee Jung Sun , Kim HwaHwan , Fitzpatrick Sara , Johnson Mary Ann
Published: June 2021

The purpose of this study is to describe subjective and objective measures of food environments in relation to food insecurity in a random sample of 138 senior center participants in northeast GA (mean age 78 years, 77% women, 41% black). Subjective food environments were measured by an interviewer‐administered survey and food resources were geocoded to census blockgroups. Around 12% of the sample were food insecure, and they were more likely to be black, less educated, and at higher nutritional and functional risk than food secure participants. Food insecure participants were more likely to live in poorer urban areas where more and different kinds of food stores were available in a closer distance than where food secure participants lived. Most of the food insecure participants reported using a supermarket most frequently for grocery shopping, and around 70% of them reported traveling <5 miles and <10 minutes to get to their frequently used supermarket. However, food insecure participants were more likely to report lower perceived availability and affordability of food stores in their community than their counterparts. These data suggest that food insecure older adults may perceive limited access to food stores irrespective of actual availability of food stores in their community, and warrant further studies to understand the challenges low‐income older adults face in the community to meet their basic food needs.
IOM‐Recommended Changes in WIC Food Packages: Responses by WIC Participants
Authors: Black Maureen , Hager Erin , Kristen Hurley , Quigg Anna , McGill Adrienne , White Nneka , Mayes Lacy
Published: June 2021

Objectives: To examine how WIC participants use the current food packages and their response to potential changes proposed by the Institute of Medicine. Methods: Data were collected through individual interviews and focus groups in 5 diverse counties in Maryland. The sample included 187 white, African American, and Hispanic WIC participants. Results: One‐third (34%) were food insecure (FI). Almost all caregivers drank 100% fruit juice and gave it to their children. Most caregivers and children ate fresh fruits and vegetables (FV), 25% ate frozen FV, and fewer than 15% ate canned FV. Bean consumption varied by ethnicity. Few English‐speakers ate beans and they did not want canned beans to substitute for peanut butter. Spanish‐speakers ate beans frequently. No caregivers had ever consumed or prepared tofu and were not interested. Caregivers did not like the taste of reduced‐fat products, “I want all the fat in my food.” Caregivers recommended that WIC increase the variety of cereals and provide wheat thins, butter, meat, tuna, ice cream, and popsicles (for teething babies). FV consumption did not differ by food security; FI caregivers reported a higher increase of FV intake if WIC provided fresh FV than did food secure caregivers, p<.05. Conclusion: Caregivers consume FV and prefer fresh products. Acceptance of reduced‐fat products, beans, and tofu may require ethnically‐sensitive education.
Embryonic Epicardial Cell Lineages: Making and Unmaking a Heart
Authors: Perez‐Pomares Jose M.
Published: June 2021

The interaction of heart muscle precursors with other non‐muscular endodermal, ectodermal and mesodermal cell populations (i.e. the pharyngeal endoderm, the neural crest ectomesenchyme, the endocardium and the epicardium, respectively) is critical to the proper morphogenesis of the heart, including the complete differentiation of myocardial progenitors into a variety of muscle types that are neither equal in origin nor equivalent in their biomechanical properties. Moreover, normal cardiac development also depends on the restriction of myocardial domains after the inhibition of the muscular potentials of the pericardiac mesoderm. Proepicardial cells, which constitute a part of the pericardiac mesoderm located at the heart inflow, and their epicardial derivatives are most relevant to heart development and viability since they give rise to both coronary blood vessels and cardiac interstitial cells, but also modulate chamber myocardial proliferation. Most interestingly, proepicardial cells can differentiate into myocardium in vitro but not under normal in vivo conditions. It is the main aim of this presentation to provide information on the transcriptional and signaling networks involved in the definition of epicardial developmental potential and fate and to discuss on their embryological significance.
Obscurin and titin as interacting partners during cardiac differentiation and remodeling
Authors: Borisov Andrei B , Westfall Margaret V , Russell Mark W
Published: June 2021

Obscurin is a recently identified giant muscle protein that binds titin, another giant muscle protein of the immunoglobulin superfamily. Both proteins, in addition to their structural domains, contain the kinase‐like domains that appear to be involved in signal transduction. Little is known about the structural relationship and the expression dynamics of these proteins during growth and adaptive reactions of cardiac muscle. The goal of this study was to comparatively investigate the localization patterns of these proteins during differentiation and remodeling of cardiac myocytes in vivo and in cell culture using high resolution confocal microscopy. We also performed the comparative analysis of obscurin and titin incorporation into nascent sarcomeres on the tips of growing myofibrils. We found that obscurin and titin incorporated into forming myofibrils relatively early, before the establishment of registered, aligned pattern of myofibril structure typical of the mature contractile system. Co‐localization of titin and obscurin at the level of the Z‐discs and their close topographical apposition at the A‐I band interfaces of sarcomeres indicate their structural interaction within these structures. The labeling patterns of obscurin and titin expression rapidly changed during structural remodeling of differentiated cardiomyocytes and appear to be one of the earliest detectable markers of this process. Interestingly, downregulation of both obscurin and titin resulted in similar changes in the structure of the contractile system of cardiac myocytes. These data suggest the synergistic involvement of these two proteins in the support of the structural integrity of the contractile apparatus in cardiac muscle. Supported by MDA3803 and NIH HL075093