bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial Not Epithelial‐Cell Expression of TNF‐α is Critical for the Development of Shock Induced Acute Lung Injury (ALI): IT vs. IV
Authors: Lomas‐Neira Joanne , Perl Mario , Soldato Doreen , Venet Fabienne , Chung Chun‐Shiang , Ayala Alfred
Published: June 2021

While it is clear that many cells in the lung can express/respond to the proximal inflammatory mediator, TNF‐α, in vitro/ex vivo, the cells affected in vivo in a complex pathological state such as hemorrhagic shock (Hem) and sepsis, remain poorly understood. To unravel these pathways, we used divergent routes of TNF‐α siRNA delivery to alternately suppress expression of TNF‐α in lung endothelial and epithelial cells. Initially, fluorescently labeled siRNA were used to assess the cellular targets of i.t. (naked siRNA) vs. i.v. (liposomal encapsulated naked siRNA) delivery. Confocal microscopy of lung tissue sections showed labeled siRNA delivered i.v., primarily in endothelial cells; while i.t., delivery showed co‐localization of fluorescence in lung epithelial (cytokeratin 18+) cells. Next siRNA against TNF‐α was administered, i.t., to C57/BL6 mice at 2‐h post Hem, 24‐h prior to septic challenge. Lung tissue from treated mice showed no significant change in levels of the chemokines, macrophage inflammatory protein‐2 and keratinocyte derived chemokine, or interleukin‐6 (IL‐6) or PMN influx. In contrast, i.v. delivery produced a significant decreased IL‐6 and PMN influx into the lungs. These findings suggest pulmonary endothelial and/or other possible vascular resident cells, not epithelial cells, play a greater role in mediating the TNF‐αresponse in a mouse model of Hem/sepsis induced ALI. (NIH HL‐73525)
The renin cell precursor: distribution and fate
Authors: Lopez Maria Luisa Soledad Sequeira
Published: June 2021

Renin‐synthesizing cells are crucial in the regulation of blood pressure and fluid and electrolyte homeostasis. These cells have been considered for a long time as terminally differentiated because they synthesize a hormone (renin), they are few in numbers, and they are restricted to a juxtaglomerular localization in the adult mammalian kidney. However, by generating knock‐in mice expressing cre recombinase in renin‐expressing cells and crossing them with reporter mice we showed that renin‐expressing cells are precursors for a variety of cells that differentiate into non‐renin‐expressing cells within and outside the kidney. These differentiated cells that descend from renin‐expressing cells consist of a subset of vascular smooth‐muscle, epithelial, and mesangial cells within the kidney. Extrarrenal descendents are found in the adrenal gland, testes, sympathetic ganglia, cartilage, bone marrow. When homeostasis is threatened, specific subpopulations of apparently differentiated cells that descended from renin cells de‐differentiate and re‐express renin in an attempt to reestablish homeostasis, and re‐differentiate when the crisis passes.
Two laboratories on Human Physiology involving active participation of undergraduate students at the University of La Reunion's Island
Authors: Bourdon Emmanuel , Tarnus Evelyne
Published: June 2021

Obesity and diabetes are associated with an increased mortality risk. In the Indian Ocean, La Reunion Island, a French overseas department, presents an increasing prevalence of obesity and diabetes. The Island provides an example of rapid urbanization over just a few decades. At the University of La Reunion, two laboratories involving undergraduate students were designed to teach the determination of body composition and the measurement of blood sugar concentration and glycemic response consecutive to a food intake. Different devices were used by the students such as skin fold calipers, impedencemetry balances, blood glucose monitoring system. Using equations, students determined the fat and total muscular masses of their body composition. Correlations were established between the students’ body mass indexes values and their fat mass percentages and between their fat‐free and muscular masses as well. A higher fat mass percentage was found in sedentary students compared with more active ones. A positive correlation was observed between the students’ glycemic response and their fat mass percentages. These laboratories provided students with the opportunity to collect data, evaluate it using statistical analysis, interpret their results in a scientific report. By these, they engage a real world problem constituted by the increasing prevalence of obesity and diabetes.
Immunoelectron microscopy of TDP‐43 in frontotemporal lobar degeneration, amyotrophic lateral sclerosis and Lewy body disease
Authors: Lin Wen‐Lang , Dickson Dennis W
Published: June 2021

TAR DNA‐binding protein of 43 kDa (TDP‐43) is a nuclear protein involved in transcriptional repression and alternative splicing. It has been shown to be a component of ubiquitin‐positive, tau‐ and á‐synuclein‐negative inclusions in neuronal soma and nuclei as well as neurites of frontotemporal lobar degeneration (FTLD‐U) and in motor neurons of amyotrophic lateral sclerosis (ALS). Recently, it has been co‐localized with Lewy bodies in Lewy body disease (LBD). In this study we use immunogold electron microscopy to study the ultrastructural features of TDP‐43‐labeled structures. The results showed that in all FTLD‐U, ALS and LBD, TDP‐43 was localized to filaments coated with granular material. Both coated and uncoated regions of the filaments were labeled. In FTLD‐U a subset of neurites filled with densely packed filaments were also labeled. The filaments have a diameter of 10–17 nm. Neurofilament and glial filaments were not labeled by TDP‐43. The data suggests that TDP‐43 is a constituent protein in filamentous inclusions in neurodegenerative diseases. Supported by NIH grant AG17216.
Changes in diastolic stress, not systolic stress, attenuate the development of load‐induced hypertrophy in FHL1 null myocardium
Authors: Raskin Anna Maria , Sheikh F. , Hoshijima M. , McCulloch A. , Omens J.
Published: June 2021

Although most studies correlate an increase in systolic stress with pressure overload hypertrophy, there is some evidence suggesting diastolic stress/strain may play the greater role. A culture system was developed in which the application of uniaxial stresses to papillary muscles from knockout (KO) mice can induce a hypertrophic response, while simultaneously assessing tissue mechanical properties. After 5 hrs of 15% stretch, muscles express hypertrophic markers ANP & BNP. By comparing the linear regressions of ANP expression verses passive or active stress we found that a higher statistical correlation exists between ANP induction and passive stress than active systolic stress. We compared the development of hypertrophy in KO mice with abnormal diastolic tissue mechanical properties. ANP gene expression in muscles from muscle LIM protein KO mice, a well characterized mouse model having significant diastolic dysfunction, was ~4 times lower when compared to controls. Four & a half LIM protein (FHL1) KO mice exhibited a blunted hypertrophic response and lower ANP levels after 35 days aortic banding. ANP induction by stretch in muscles from FHL1KO mice was also reduced (P<0.05). FHL1KO muscles exhibited greater diastolic tissue compliance, with no change in systolic mechanics. We conclude that changes in passive mechanics correlate with attenuated development of pressure overload hypertrophy in FHL1KO mice.
Crystal structure and nanoanatomy of the E. coli RecA protein
Authors: Roca Alberto I , Larson Steven , McPherson Alexander
Published: June 2021

The E. coli RecA homolog has been previously crystallized in four conformations (Xing & Bell 2004). We have determined the crystal structure of the E. coli RecA protein to 2.5Å in novel magnesium solution conditions. To facilitate a clear discussion of structure, we introduce a nomenclature based upon our description of RecA protein “nanoanatomy”. Namely, the anterior face of the RecA monomer is defined as the side pointing toward the filament interior. We also propose names for the “bioinformatic elements” of the RecA protein as visualized by ProfileGrids. Previous E. coli RecA structures had disordered L1/L2 loops and the last 25 residues of the C‐terminus. By contrast, low resolution structures of these regions was revealed by the Mycobacterial RecA homologs (Vijayan & co‐workers 2000‐2007). We propose a model for these parts of the E. coli RecA protein. First, the L2 loop follows the filament right‐handed helical path. Second, within the monomer posterior groove we observe the C‐terminus. In general, these E. coli RecA loop conformations are opposite from seen in the Mycobacterial RecA structures. [AIR supported by a NIH Diversity Supplement and a UC President's Postdoctoral Fellowship.]
Human SFMBT binds the N‐terminal tail of histone H3 to induce transcriptional repression of specific target genes
Authors: wu shumin , Rice Judd
Published: June 2021

We recently discovered that human SFMBT (hSFMBT), which contains a tandem array of four conserved MBT domains, is a potent repressor of transcription. In addition, we found that hSFMBT partitions to the nucleus where it strongly associates with the insoluble chromatin of the nuclear matrix and selectively binds the N‐terminal tail of histone H3. Importantly, we discovered that all four MBT repeats of hSFMBT were sufficient for nuclear matrix‐association, N‐terminal tail H3 binding, and required for transcriptional repression. These findings indicate that the tandem MBT repeats form a functional structure required for biological activity. We hypothesize that hSFMBT is targeted to specific genomic regions to maintain a transcriptionally repressive state. Consistent with this, we have recently identified several candidate genes regulated by hSFMBT and are currently verifying these findings. In addition, we recently found that hSFMBT exists in an ~700 kDa complex using conventional chromatography techniques. Ongoing studies aim to identify these proteins and determine their functional significance.
The Mitochondrial Biogenesis Regulator PGC‐1alpha is Degraded by the Proteasome and Calpain Pathways in Renal Cells
Authors: Rasbach Kyle A. , Green Peter T. , Schnellmann Rick G
Published: June 2021

Peroxisome proliferator activator receptor γ coactivator 1α (PGC‐1 α) is a transcriptional coactivator known to mediate mitochondrial biogenesis. While PGC‐1α transcription is regulated by a variety of signaling cascades including, p38 MAPK, CAMK, calcineurin A, and nitric oxide, there has been little investigation into the mechanisms of PGC‐1α degradation. The goal of this study was to determine the mechanisms responsible for PGC‐1α degradation in renal proximal tubular cells (RPTC). Amino acid sequence analysis of the PGC‐1α protein revealed three regions enriched in PEST sequences, predictive of proteolysis by calpains and/or the proteasome. Under basal conditions, treatment with the protein synthesis inhibitor cycloheximide, to block PGC1α synthesis, resulted in the rapid degradation of PGC‐1α with t1/2 of 38 min. This degradation was blocked by the calpain and proteasome inhibitor, MG‐132 (10 μM) and the specific proteasome inhibitor epoxomicin (10 μM), but not the specific calpain inhibitor calpeptin (100 μM). Similarly, treatment with MG‐132 and epoxomicin promoted the accumulation of both adenoviral expressed and endogenous PGC‐1α. To determine if the Ca2+ activation of calpains results in cleavage of PGC‐1α, RPTC over‐expressing PGC‐1α were lysed and the addition of Ca2+ resulted in the degradation of PGC‐1α in 5 min. This degradation was blocked by the calpeptin (100μM) but not epoxomicin (10μM). In summary, this investigation reveals two distinct mechanisms of PGC‐1α regulation; 1) basal turnover of PGC‐1α is controlled by the proteasome degradation pathway and 2) increased Ca2+ levels result in proteolysis of PGC‐1α through calpain.
Regulation of CDKN1A expression in keratinocytes by Distal‐less 3
Authors: Pietroni Valentina , Radoja Nadezda , Rivera Yesenia , Stimpson Sarah Jo , Anderson David Eric , Blumenberg Miroslav , Morasso Maria I
Published: June 2021

The balance between proliferation and differentiation has always been a central question in development. Homeobox genes have been shown to act directly on the regulation of cell cycle checkpoints, inducing or preventing cells from exiting the cell cycle. The homeodomain transcription factor Dlx3 is expressed in the differentiated layers of the stratified epidermis. We showed that ectopic expression of Dlx3 in the proliferative basal layer of the epidermis in transgenic mice, lead to premature differentiation of the keratinocytes. To determine the role of Dlx3 in the control of the cell cycle, we analyzed by microarray the gene expression profile of keratinocytes transduced with a retroviral vector expressing Dlx3. The overexpression caused an arrest of the cell cycle in G1 phase due to an upregulation of CDKN1A. Performing Luciferase Assays, EMSA and ChIP, we demonstrated that CDKN1A is a direct target of Dlx3. We confirmed the upregulation of CDKN1A and downregulation of Cyclin D in synchronized cells using a PAM212 Dlx3 Tet‐on system. We are assessing CDKN1A regulation by Dlx3 using shRNA. These data demonstrate an important role of Dlx3 in the control of the cell cycle.
TLR‐2 agonist enhances the development of autoimmune diabetes
Authors: Lukic Miodrag L , Mensah‐Brown Eric , Shahin Allen
Published: June 2021

Toll‐like receptor 2 agonist (TLR2) BLP (bacterial lipoprotein, PAM3CSV‐4) was found to enhance IL‐12 and INF‐α synthesis to ameliorate Th‐2 dependent pathology in experimental asthma and to modulate the functions of CD4+ CD25+ regulatory cells. TLR‐2 deficiency in NOD mice confers significant protection against the development of diabetes. Multiple low doses (40 mg/kg b.w) of streptozotocin given for 5 consecutive days, β‐cells (MLD‐STZ x 5 ) induce accumulation of apoptotic β cells and development of autoimmune diabetes in susceptible C57BL/6 male mice. However administration of 4 low doses of STZ (MLD‐STZ x 4) do not achieve such an effect and the number of apoptotic and necrotic cells was significantly lower by the end of (MLD‐STZ x 4) treatment than in (MLD‐STZ x 5) treated group. We have used (MLD‐STZ x 4) model to test the effect of TLR‐2 agonist on diabetes induction. We have clearly demonstrated that BLP facilitate diabetes induction when given in single daily i.p. injection of 200μg/mouse on days 5 – 10 after initiation of STZ treatment as evaluated by clinical and histological criteria. This enhancing effect was accompanied by the increased expression of TNF‐α, INF‐γ and IL‐17 in the draining pancreatic lymph nodes. The results are compatible with the notion that more effective presentation of islet specific autoantigens in TLR‐2 agonist treated group leads to autoimmune diabetes in this model. (Supported by UAE University Grant)
Serum autoantibody profile of patients with age‐related macular degeneration
Authors: Morohoshi Kei , Patel Nishal , Aye Cho Cho , Ohbayashi Masaharu , Ono Santa Jeremy
Published: June 2021

Age‐related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial countries. Recent findings indicate that both genetic and immunological factors are involved in the pathogenesis of AMD. Autoantibodies in particular have been implicated in AMD pathogenesis, yet only a few antibodies have been identified in sera from patients with AMD. In order to reveal an autoantibody profile for AMD and identify biomarkers for progression of this disease, we incubated an antigen microarray with serum samples from patients with AMD and healthy controls. Sera from the AMD group contained high levels of IgG autoantibodies to some antigens including cyclic nucleotide phosphodiesterase and proliferating cell nuclear antigen, when compared to the normal group. Moreover, the IgG/IgM ratio for antibodies to some systemic antigens correlated with the stage of AMD. Our data suggest that these IgG autoantibodies and the ratio may be used as biomarkers for AMD. Further studies are needed to clarify whether the autoantibodies directly cause AMD or are secondary products in the progression of AMD. This work is supported by the Dobbs Foundation, Special Trustees of Moorfields Eye Hospital and the NIH.
Protection against autoimmune diabetes by viral infection
Authors: Filippi Christophe , Oldham Janine , Bresson Damien , Christen Urs , Wolfe Tom , von Herrath Matthias
Published: June 2021

Type 1 Diabetes (T1D) is an autoimmune disease that results from the selective destruction of insulin‐producing beta cells in the pancreas. While it is generally believed that viral infections are responsible for inducing autoimmunity in individuals at risk, experimental evidence indicates that viruses can efficiently prevent T1D. We have identified two mechanisms by which acute lymphocytic choriomeningitis virus (LCMV) infection hampers autoimmune diabetes development in the mouse.

The first mechanism is the direct consequence of the early release of inflammatory mediators following LCMV challenge which rapidly confer leukocytes from infected mice the capacity to diminish T1D. The second mechanism involves longer‐term modification of CD4+CD25+ regulatory T cells which become capable of preventing both spontaneous and virally induced T1D as a consequence of TGF‐beta production. Importantly, hampering of autoimmunity by viral infection does not appear to impair antiviral immunity and viral clearance.

These findings provide novel mechanistic insight into the ability of viral infection to abort autoimmune diabetes. Induction of such mechanisms during infection may account for the capacity of viruses to prevent T1D as well as other autoimmune disorders.
LPS‐induced TNFα production by macrophages is suppressed by a soluble product from the adult tapeworm, Hymenolepis diminuta
Authors: Johnston Michael , Catarino Michael , Wang Arthur , Cho Suzanne , Phan Van , McKay Derek
Published: June 2021

Helminth parasites actively regulate their hosts’ immune response. Thus parasite‐derived molecules have the potential to be used to skew or suppress immune responses in humans as a way to treat immunopathology and disease. Seeking to exploit this we hypothesized that a product from H. diminuta would suppress macrophage activation. The human THP‐1 macrophage cell line was treated with LPS ± a high molecular weight fraction (HMWf: >50kDa) of H. diminuta. The HMWf reduced macrophage activation as assessed by TNFα and IL‐6 production in a time‐ and dose‐dependent manner. The ability of THP‐1 cells to phagocytose E. coli was unaffected by HMWf. RT‐PCR for the mannose receptor (up‐regulated on anti‐inflammatory macrophages) and Toll‐Like Receptor 4 (LPS receptor) mRNA revealed no differences between groups, indicating that the HMWf does not induce an alternatively activated macrophage or interfere with TLR4 expression. A HMWf from excretory/secretory (E/S) products from H. diminuta also reduced LPS‐induced TNFα production. The ability of the adult worm HMWf or the E/S products to block TNFα production by THP‐1 cells was insensitive to boiling or treatment with proteinase K. We conclude that a heat stable HMW product(s) from H. diminuta is a potent suppressor of macrophage activity, and that purification of this factor could serve as a template for drugs to block inflammatory disease. Funded by CCFC, CIHR & CAG.
Addressing Health Disparity Concerns among Residents at risk for Cardiovascular Disease in an Alabama Black Belt County
Authors: Pace Ralphenia Diggs , Dawkins Norma L
Published: June 2021

The occurrence and the disparities of chronic diseases among African Americans continue to be areas of concern among nutrition and health researchers. Cardiovascular disparities in the Black Belt counties are higher than the state and the national averages. This survey was designed to 1) determine the readiness of individuals to participate in a community faith‐based nutrition education program; and 2) to uncover what were the perceived health concerns of residents in the community. In preparation for implementation of a nutrition education intervention program designed to reduce cardiovascular disease among African Americans, a community opinion questionnaire (COQ) was pilot tested and mailed to potential participants.

Ninety‐nine (99%) of the respondents perceived community programs to be important. While 96.1% felt comfortable participating in a community outreach program and 89.3% expressed their commitment to the end. The trust factor for research still posed a problem but 87.5% agreed to participate if it was conducted by Tuskegee University. They relied on physicians (35.8%), churches (28.5), and their respective spouse (14.5%) to obtain information about their health. Approximately eighty six percent (85.9%) desired to change dietary habits with 54.3% worried about their health; however, only 47.5% exercised regularly.
Assessment of saproby by algae in artifical lake “BADOVC” nearby Prishtia city in Kosova
Authors: Kurteshi Kemajl , Vehapi Idriz , Gecaj Abdulla , Millaku Fadil , Muzaferovic Sefkija , Ismaili Muharem
Published: June 2021

During the summer 2002 we investigate the algae of the artificial lake “Badovc” nearby the Prishtina city, which supply yhe city of Prishtina. We taken the samples from 9 station at lake. We determinate the composition of the algae: 6 species belong divission Cyanophyta, 41 species belongs Bacillariophyta, 3 species Euglenophyta and 9 species Chlorophyta, altogether 59 species. According the bioindicator species we are done the qualitative estimation of waters artificial lake. Based on the presence of species as saprobiologic bioindicator and saprobic level , the waters of lake Badovc belongs the second level of bonity respectively beta‐mesosaprob
Contemporary Pattern of Colostrum Consumption, Complementary Food Introduction and Dietary Diversity among Infants of a Rural Guatemalan Village.
Authors: Hernandez Liza , Campos Raquel , Solomons Noel W.
Published: June 2021

Background

As the food pattern and micronutrient content of complementary foods is widely deficient in low‐income societies, uncovering opportunities for favorable interventions is vital.

Objectives

To describe colostrum use, introduction of complementary foods, and dietary diversity after 6 mo in a rural, Guatemalan setting.

Methods

70 mothers of infants aged 6–11 mo in Santo Domingo Xenacoj, Guatemala were enrolled, interviewed with a structured questionnaire, and underwent 24‐h recalls of the infant's intake of foods and beverages (other than human milk {HM}) on 3 occasions.

Results

The 70 infants averaged 8.3+/−2.0. mo at enrollment. 62 of 70 infants (89%) reportedly had consumed colostrum. 19 different items were reported as the initial food, with white rolls (19%), formula (13%), rice (10%), potato (9%) and Incaparina gruel (7%), constituting the 5 most common first foods. 40 infants completing three 24‐h diet records consumed from 2 to 23 different non‐HM items over the 72 h covered. These items provided from 65 to 540 kcal/d, complementing the energy provided by HM (which was not measured).

Conclusions

Complementary feeding practices and the nutrient delivery from complementary foods require improvement in this community setting.

Sponsored by Sight & Life
Food Insecurity and Social Capital of Impoverished Women from Rural Appalachian Ohio: A Pilot Study
Authors: Stiefel Alyson M. , Holben David H. , Holcomb John P. , Hazen Crystal , Struble Celia J.
Published: June 2021

Food security (FS) and social capital (SC) were studied in Food Stamp‐eligible women at least 18 years with at least 1 child<18 years living in rural Appalachian Ohio and were randomly assigned to produce (home delivery, $60 fresh produce for 4 weeks) [n=30, 90.9% retention rate (RR)] and control ($60 food/fuel gift cards) (n=31, 93.9% RR) groups. Participants (35+/−9 years; 4+/−2 household members; monthly income, $913+/−728) completed pre‐ and post‐interviews. After 4‐weeks, SC did not change (t‐test, p=0.742); however, both household FS (t‐test, p=0.028) and adult FS (t‐test, p=0.020) decreased among the produce group. Child FS did not change (t‐test, p=0.095). For all participants (n=61), SC was not associated with household FS (p=0.138), adult FS (p=0.118), or child FS (p=0.128). The negative impact of produce delivery on FS may be due to lack of nutrition education and/or being unfamiliar with the produce, prohibiting household use. The short duration and small sample size of the study may have contributed to both FS and SC trends observed. Future studies should examine these constructs over the entire growing season to better understand the impact of home‐delivered produce on SC and FS.
Promoting low‐energy dense nutrition educations results in improved dietary habits and diet quality assessed by using Diet Quality Index‐International (DQI‐I) in college women
Authors: Yun Hee Kyung , Lee Seung Hee , Chang Namsoo
Published: June 2021

Effectiveness of nutrition education is assessed by various indicators such as dietary habit change, weight difference and etc. College women who participated in an 8 wk weight management program focused on nutrition education promoting low‐energy dense were evaluated to identify measurable changes. Dietary 24‐h recalls was assessed by the Computer Aided Nutritional analysis program. The 145 participants’ mean age was 21.9±3.1yrs and mean body mass index was 23.2±2.3kg/m2. Upon completion, 89 subjects lost weight on an average of 1.3kg. The weight lost (WL) group had improvements in dietary habits specifically with significantly reduced intake of energy, carbohydrate, cereals and grain group, fruit group, meal distribution of dinner, snack and energy distribution of carbohydrates. However, intake of fiber, protein, vegetables, meat and fish group, meal distribution of breakfast, lunch, energy distribution from protein and nutrient density of vitamins and minerals increased significantly. The INQ of all nutrients, protein source variety score, adequacy score of fiber, moderation score of sodium, empty calorie food and total DQI‐I score increased significantly. In addition, the serum triglyceride decreased significantly in the WL group. These results show that low‐energy dense nutrition education may help improve dietary habit and diet quality in college women.
Assessing determinants of fish consumption in worksite cafeteria customers
Authors: Keim Kathryn Sarah , Clement Jennie
Published: June 2021

Study objective was to determine the association among fish intake and the following: demographic characteristics; fish and heart disease knowledge; health beliefs; and fish preferences using Health Belief Model (HBM) and Social Marketing Model (SMM). A 51‐item questionnaire was returned by 473 worksite cafeteria customers (57% response rate). Twenty‐seven percent of respondents ate fish in the cafeteria (fish eaters). Significantly more respondents over age 40 (38%) compared to those 40 and younger (17%) (p=0.000) were fish eaters. Significantly more fish eaters (80%) compared to non‐fish eaters (62%) knew the American Heart Association recommends all people consume two servings of fish/week (p=0.000). There were no significant associations between health beliefs and fish intake. Ninety‐four percent of fish eaters had a high fish preference score (higher score means likes all kinds of fish) compared to 55% of non‐fish eaters had a low fish preference score (p=0.000). HBM constructs may not be appropriate to use while the product construct of the SMM should be considered when developing an intervention to increase fish consumption of worksite cafeteria customers. Study methods were approved by Rush University Institutional Review Board for Human Subjects. Project funded by Department of Food and Nutrition Services, Rush University Medical Center.
Effect of addition of menthol to a drink on voluntary fluid and carbohydrate intake during exercise in humans.
Authors: Okada Sachiko , Tai Shinji , Kondo Emi , Okamura Koji
Published: June 2021

The purpose of this study was to investigate if the cold sense of menthol facilitates voluntary fluid and carbohydrate (CHO) intake during exercise in humans. Eighteen women's hockey player performed a routine training session were given 3 beverages : water (W), 5% CHO drink (C; 5% CHO, 0.1% citric acid, 0.1% NaCl) and 5% CHOwith menthol drink (MC; 5% CHO, 0.1% citric acid, 0.1% NaCl, 0.1% menthol). The subjects chose these drinks freely during the training and the intake of each drink was measured after the training. The subjects were asked to answer a visual‐analog‐scale (VAS) questionnaire on the feelings on each drink. Although the intake of each drink did not differ significantly, the intake of C and MC tended to be greater than W. The subjects fell into three groups according to their most favorite drink; W (PW, n=3), C (PC, n=7), MC (PMC, n=8). Fluid and CHO intake of PC and PMC was calculated as the sum of the most favorite drink and water. The ratio of water intake was higher in PC than PMC (43.0% (SD 34.9) vs 8.7 (6.1), P < 0.05). Consequently, C was diluted more compared to MC. As a result CHO concentration was PMC > PC (4.6% (SD 0.3) vs 3.6 (0.9) , P < 0.05). VAS data showed that sweetness was stronger in MC and C than W (P < 0.05), and tended to be lower in MC than C. These results suggest that the cold sense of menthol reduces sweetness which would avoid diluting a drink so that larger amount of CHO could be supplied during exercise, which would be beneficial to improve physical performance.
Deficit of Prepulse Inhibition in Mice Caused by Dietary n‐3 Fatty Acid Deficiencies.
Authors: Fedorova Irina , Hussein Nahed , Salem Norman
Published: June 2021

Docosahexaenoic acid (DHA, 22:6n‐3) is the most abundant polyunsaturated fatty acid in the brain and plays an important role in learning and memory. It was shown that profound DHA deficiency led to modification in dopamine and serotonin systems. Prepulse inhibition is deficient in psychotic disorders such as schizophrenia and can be disrupted in animals by dopamine and serotonin agonist administration. DHA and eicosapentaenoic acid (20:5n‐3) are biosynthesized from α‐linolenic acid (LNA, 18:3n‐3), a shorter chain n‐3 fatty acid precursor or obtained with a diet.

Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response in C57Bl6 mice. Mice were fed for two generations four diets with different levels of n‐3 fatty acids: n‐3 deficient, containing 0.07% of LNA; low LNA (0.38% of total fatty acids); high LNA (4.8%); and high n‐3 diet, containing 0.38% of LNA, 2% DHA and 2% EPA. N‐3 deficient and low LNA diets caused a substantial deficit in PPI compared to the high n‐3 diet, whereas the high LNA diet induced a less pronounced, but significant PPI reduction. These are the first data that differentiate in rodents the effects of a high LNA diet from one with added EPA/DHA. The rather small increment in brain DHA content is thus associated with a functional difference manifested in sensorimotor behavior.
Correlation between adiponectin polymorphisms and non‐alcoholic fatty liver disease with or without metabolic syndrome in Chinese population
Authors: Wang Zhongli , Xia Bing
Published: June 2021

Background: To investigate the effect of single nucleotide polymorphisms (SNPs) 45 and 276 of the adiponectin gene on non‐alcoholic fatty liver disease (NAFLD) with or without metabolic syndrome.

Methods: A total of 165 NAFLD, 83 NAFLD with metabolic syndrome and 160 healthy controls were investigated from Chinese population. Genotypes were assayed by PCR‐restriction fragment length polymorphism. Plasma adiponectin and insulin levels were determined by enzyme‐linked immunosorbent assay and radioimmunoassay, respectively. Insulin resistance (IR) was evaluated by using HOMA‐IR (homeostasis model assessment of insulin resistance).

Results: NAFLD with metabolic syndrome had further extent of IR and hypoadiponectinemia. No association of SNP45 or SNP276 was found in NAFLD or NAFLD with metabolic syndrome. In various subgroup analysis, subjects carrying the G allele of SNP45 showed higher levels of triglyceride (TG), fasting blood sugar (FBS), HOMA, body mass index (BMI) and alanine transaminase (ALT), as well as lower plasma adiponectin levels. In normal weight group of SNP276, subjects carrying the G allele showed higher HOMA and subjects carrying the T allele showed lower BMI.

Conclusions: Our study observed further hypoadiponectinemia and IR in NAFLD with metabolic syndrome. The T45G and G276T of the adiponectin gene may not be the important determinants of NAFLD in Chinese people, but some of them still influence serum ALT, BMI, IR, lipid and glucose metabolism and plasma adiponectin concentration
The effects of uncoupling protein 1 and β3‐adrenergic receptor gene polymorphisms on weight loss and lipid profiles in obese premenopausal women
Authors: Lee Sang Sun , Kim Jung Yun
Published: June 2021

The purpose of this study was to investigate whether the A–G polymorphism at position −3826 bp in the 5′ flanking domain of the uncoupling protein 1 (UCP1) gene and the Trp64Arg mutation of the beta 3 adrenergic receptor (β3‐AR) gene were associated with differences of weight loss and lipid profile in obese premenopausal women exposed to a low calorie meal replacements over a period of 6 weeks. Forty women between the ages of 20 and 35 were randomly divided into two groups who consumed one of two low calorie meal replacements containing either white rice (WR group) or mixed rice (BRBL group). UCP1 gene polymorphisms did not show an association with body weight change and body mass index (BMI), blood glucose concentration, triglycerides, total cholesterol and high‐density lipoprotein cholesterol after 6 weeks in the WR group. However, there were significant differences in body weight (P = 0.041), BMI (P = 0.027), blood glucose concentration (P = 0.047) between carriers and non‐carriers of G allele in the BRBL group after 6 weeks. These results which was shown only in BRBL group is considered to be caused by weight loss happened more in BRBL than in WR group. The β3‐AR polymorphism showed no apparent affect on these parameters. Although some studies on obese subjects have shown an effect of the UCP1 and β3‐AR gene polymorphism on the susceptibility to obesity, the results of this study have failed to mention any associations.
Comparison of Four Commercially Available Zinc Supplements for Performance in a Zinc Tolerance Test
Authors: DiSilvestro Robert A , Swan Melinda
Published: June 2021

Various zinc complexes have been used for supplements and food fortifications, but direct comparisons of bioavailability in humans are few. In the present study, in 12 young adult women, four zinc complexes (oxide, picolinate, gluconate, and glycinate) were compared for acute uptake using a zinc tolerance test (plasma zinc changes hourly for 4 h after a single zinc dosing), and two related measures (erythrocyte zinc and activity of the zinc enzyme 5′‐nucleotidase over the same 4 h period). Plasma zinc rankings based on area under the curve, as well as by rank results per person, were: glycinate > gluconate > picolinate=oxide. Erythrocyte zinc rankings based on area under the curve, as well as by rank results per person, were: glycinate > picolinate >oxide > gluconate. None of the supplement significantly increased 5′‐nucleotidase activities at any of the time points. In summary, zinc glycinate showed the best acute uptake of the four complexes tested. Disclosure Note: R DiSilvestro has a consultant retainer agreement with Albion Laboratories, who supplied zinc glycinate, but this was not true when the study was done, nor did Albion fund this study.
Genetic variations in ventral midbrain iron influence diurnal locomotor activity and body temperature in BXD mice
Authors: Unger Erica Lynn , Sterling Matthew E , Jones Byron C , Beard John L
Published: June 2021

There is a close association between ventral midbrain (VMB) iron content and nigrostriatal/mesolimbic dopamine function, and changes in dopamine neurotransmission are known to influence motor activity across the diurnal cycle. In this study, we investigated whether genetic variations in VMB iron influence motor activity, particularly during the light/dark transitions. VMB iron content was determined in 30 strains from the BXD/Ty RI panel. Subsequently, 6 strains were chosen based on their relative high (strains 1 and 34), middle (strains 31 and 40) or low (strains 14 and 21) VMB iron levels. At four months of age, home cage activity and body temperature were measured in these 6 strains across the diurnal cycle. Compared to the other strains, Strain 31 showed lower activity counts during the dark phase, and acrophase and bathyphase were shifted 2 hr earlier in Strain 14. Within the four hours surrounding the light transition phases, activity increased during the light to dark transition and decreased during the dark to light transition at a similar rate as body temperature in most strains. Strains 14 and 21 (low VMB iron) and Strain 31 (mid VMB iron) showed blunted activity and temperature changes during the dark to light transition compared to strains with higher VMB iron (34 and 1). These results suggest that activity and body temperature during the transitional phases may be influenced by ventral midbrain iron content.
Zyflamend®, a multi‐herb extract with anticancer properties, promotes cell cycle arrest in advanced human prostate cancer cells
Authors: Huang E‐Chu , McEntee Michael F. , Whelan Jay
Published: June 2021

Zyflamend® is an extract of multiple herbs shown to inhibit the progression of prostate cancer in previous case‐reports, but the mechanisms of action are not known. We hypothesized that Zyflamend® inhibits cell growth by inducing cell cycle arrest and cell death. In this study, the cell cycle inhibitory effect of Zyflamend® was examined using 22Rv1 and PC3 cells, both androgen‐independent human prostate cancer cell lines. Cells were grown in RPMI 1640 with 10% fetal bovine serum at an initial concentration of 104 cells/well. Cell proliferation was measured by MTT assay. Following 2 and 4 days treatment with Zyflamend® (0, 20, 40, 80, 100, 150ug/ml), cell proliferation was reduced in a dose dependent manner in PC3 cells and 22Rv1 cells compared to the control treated cultures. Quantitative RT‐PCR and western blot analysis were used to determine if Zyflamend® modified expression of genes related to cell cycle signaling and apoptosis. It was shown that Zyflamend® inhibited AKT phosphorylation activity. Decreasing phospho‐AKT increases cell cycle inhibitory p21 activity and enhances p27 transcriptional regulation. Preliminary results also suggested Zyflamend® increased p21 and p27 expression at transcriptional level. This research is funded by a grant from New Chapter, Inc. Brattleboro, VT., and in part from the TN Agriculture Experiment Station, University of Tennessee, Knoxville, TN.
HPLC Analysis of Curcuminoids in Dietary Supplements and in vitro Digestion Fractions
Authors: Craft Neal E. , Chitchumroonchokchai Chureeporn , Failla Mark L , Bhagavan Hemmin N
Published: June 2021

Curcumin (Cur), demethoxycurcumin (DMC), and bis‐demethoxycurcumin (BDMC) are the main curcuminoids in Curcuma longa used to prepare the spice turmeric. Cur has been shown to reduce the risk of cancer, inflammation and Alzheimers. As such, it has become increasingly popular in foods and dietary supplements. To examine content and bioaccessibility of commercial Cur products, we developed and validated an HPLC method to measure Cur and metabolites. Dietary supplements were processed via an in vitro digestion (simulated gastric and small intestinal phases) and Caco‐2 cellular uptake (Chitchumroonchokchai et al., J. Nutr. 2004). Cur, DMC, BDMC were monitored at 425nm for sensitive detection and 280nm was monitored to detect the internal standard, Flavone, and cellular metabolites of curcuminoids. Three products were tested containing from 10% to 95% curcuminoids. The micellarized Cur was stable in cell culture medium for at least 4 hrs. Transfer of Cur from the supplements to micelles during the small intestinal phase of digestion varied markedly between the two products. Micellarization was more efficient as polarity increased, i.e., BDMC> DMC>Cur. Efficiency (%) of incorporation into micelles was higher for Curcu‐Gel™ than Turm’Brite 10% sd Cur, 29.1% vs 8.7%. Cur in synthetic micelles was taken up by the cells in a time and concentration dependent manner. (Supported in part by Tishcon Corp., Westbury, NY)
Effects of green tea or Sasa borealis bamboo on plasma lipids, platelet aggregation, erythrocyte Na efflux and bone density in ovariectomized rats
Authors: Ryou Sung Hee , Kim Kyu Il , Kang Young Hee , Kang Jung Sook
Published: June 2021

This experiment was conducted to investigate the effects of Sasa borealis bamboo and green tea on erythrocyte Na channels, platelet aggregation, plasma and liver lipids in ovariectomized (OVX) rats. Thirty ovariectomized rats and ten sham rats at age of 10 weeks were fed 10% bamboo or green tea for four weeks. The final body weight was significantly increased in OVX‐control compared to the sham‐control (p<0.01) and significantly decreased in OVX‐green tea compared to the OVX‐control (p<0.01). HDL‐cholesterol was significantly decreased in OVX‐control and OVX‐bamboo compared to sham‐control (p<0.01) without difference in total cholesterol. Plasma triglyceride of OVX‐green tea was significantly lower than those of sham‐control or OVX‐control (p<0.01). Liver triglyceride of OVX‐control was significantly increased compared with sham‐control (p<0.01), and liver triglyceride of OVX‐green tea was significantly decreased compared with OVX‐control or OVX‐bamboo (p<0.01). Platelet aggregation was lower in OVX‐control compared with sham‐control, but no statistical difference among groups. Na‐K ATPase was increased and Na‐K cotransport was decreased in OVX‐control compared with sham‐control. Na‐K ATPase in OVX‐green tea was significantly decreased compared with OVX‐control (p<0.01) and Na‐K cotransport in OVX‐bamboo and OVX‐green tea was significantly increased compared with OVX‐control (p<0.05). Bone density of OVX‐control was significantly lower than sham‐control (p<0.05). Present study showed that ovariectomy caused an increase in body weight and liver triglyceride and green tea was effective in lowering body weight and triglyceride in ovariectomized rats.
Rosette‐forming glioneuronal tumors: a report of three cases.
Authors: Hattab Eyas M. , Al‐Khatib Sohaib M , Vakili Saeed T , Witt Thomas C , Smith Jodi L , Boyce Hayden , Malik G M , Wilson Jon D
Published: June 2021

Rosette‐forming glioneuronal tumor of the fourth ventricle (RGNT‐4th) is a newly recognized entity by the 2007 WHO classification. Similar rosette‐forming neuropil islands have been described in infiltrative gliomas at sites other than the 4th ventricle (RGNT). In the latter, rosette formation does not seem to impart the same favorable prognosis as in the WHO grade I RGNT‐4th. We describe three examples of RGNTs occurring outside the 4th ventricle. Tumors were located in the right frontal lobe, cerebellar vermis away from the 4th ventricle and cervical spinal cord. Radiographically, the tumors appeared as well‐circumscribed, solid masses with focal contrast enhancement. All three tumors were characterized by extensive well‐formed rosette formation surrounding neuropil islands. The latter stained intensely with synaptophysin and negatively for GFAP. MIB‐1 labeling was virtually undetectable. The glial component was characterized as low‐grade astrocytic in two cases, and as infiltrative oligodendroglial‐like in another. The oligodendrolial component did not show 1p/19q co‐deletion on FISH analysis. Ultrastructural examination showed some of the cells to have secretory granules, while others had processes filled with glial filaments. All three patients remain recurrence free approximately two years following surgery. The striking morphologic resemblance between RGNT‐4th and RGNT suggests that these are probably the same entity; even if one chooses to designate them both as mixed glioneuronal tumors or alternatively as glial neoplasms with divergent differentiation.
Examination of blood‐brain barrier (BBB) integrity in a mouse brain tumor model
Authors: On Ngoc Hong , Mitchell Ryan , Savant Sanjot , Miller Donald Wayne
Published: June 2021

The present study examines, on a functional and biochemical level, brain tumor‐induced alterations in capillary endothelial cells forming the blood‐brain barrier (BBB). Tumors were induced by injecting Lewis Lung carcinoma (3LL) cells into the right hemisphere of female Balb/c mice. Changes in BBB permeability were assessed at various stages of tumor development, using both magnetic resonance imaging (MRI) and radiolabeled permeability markers. The expression of P‐glycoprotein (P‐gp) in the BBB was also evaluated using Western Blot. Median mouse survival following 3LL injection was 15 days. Tumor volume progressed from 1.38 mm3 on day 7 to approximately 78 mm3 on day 15. Histological and MRI analysis indicated the resulting tumor mass was restricted to the right hemisphere. The permeability of the BBB to 3H‐mannitol was similar in both hemispheres at 7 and 10 days post‐injection. At day 12 and 15, significant increases in BBB permeability was observed. The alterations in BBB permeability were associated with an increase in cerebral vascular volume, but P‐gp expression was unaffected at all stages of tumor development. The BBB is largely intact during tumor development with disruptions only observed at the later stages. Furthermore, the BBB expression of P‐gp is unaffected by tumor progression despite an increased angiogenesis in the tumor bearing hemispheres.

Funding support provided by PHS Grant R01‐CA93558.
In situ hybridization for fungal ribosomal RNA sequences using locked nucleic acid (LNA) probes
Authors: Montone Kathleen Theresa
Published: June 2021

LNA are modified RNA nucleotides where a ribonucleoside is linked between the 2′‐oxygen and the 4′‐carbon atoms with a methylene unit. LNA nucleotides exhibit increased thermal stability. ISH utilizing LNA probes targeting rRNA sequences has not been described. ISH using 3′ biotin‐labeled LNA probes (50% DNA/50% LNA) targeting Aspergillus, Zygomyces, Candida, and Blastomyces rRNA sequences was performed on culture proven paraffin‐embedded cases of Aspergillus, Zygomyces, Candida, and Blastomyces using the Microprobe staining system. The tissues were dewaxed, cleared, rehydrated and digested with pepsin. The probes were applied to the tissue sections, heated briefly, hybridized at 50°C and washed with 2XSSC. The hybrids were detected using anti‐biotin‐alkaline phosphatase followed by Permanent Red chromogen. The ISH assays detected the appropriate fungal pathogens in FFPE tissues. ISH using LNA probes targeting fungal rRNA sequences can be used for speciating fungal pathogens in paraffin‐embedded tissues. These tests could be useful when fungal pathogens are observed in tissue but cultures are negative or have not been performed.