bluuebunny/crossref_metadata_2025 huggingface dataset:
Does arm swing provide mechanical and metabolic benefits during human running?
Authors: Arellano Christopher John , Look Nicole E , Kram Rodger
Published: June 2021

Previous research has shown that the primary function of arm swing in running is to counteract the angular momentum (about the vertical axis) generated by the swinging legs, but with no apparent benefit in reducing the demand for metabolic power. We investigated the mechanical and metabolic consequences of restricting arm swing. We hypothesized that restricting arm swing would increase torso rotation (a compensatory strategy to counteract the angular momentum generated by the swinging legs) and thus increase metabolic power demand. Thirteen subjects ran at 3 m/s for randomized conditions of normal arm swing, arms held behind the back (Back), arms held across the chest (Chest), and arms clasped on top of the head (Head) while we measured the 3‐D motions of the body and net metabolic power (W/kg). Compared to running with normal arm swing (32±2 deg, mean ± sem), subjects modified upper body motion by significantly increasing torso rotation by 12.9% (Back; p < 0.05) and 43.2% (Chest; p < 0.05). However, torso rotation was not significantly greater for the Head condition (7.2%; p = 0.33). Compared to running with normal arm swing (9.84±0.17 W/kg), restricting arm swing increased the net metabolic power demand by 2.9% (Back), 8.8% (Chest), and 13.3% (Head; all p's < 0.05). We conclude that normal arm swing provides both mechanical and metabolic benefits by minimizing the amount of torso rotation needed to counteract the angular momentum of the swinging legs.
Increased pentobarbital insensitivity in hypoglossal (XII) motoneurons during late pregnancy is consistent with increased epsilon subunit expression in GABAA receptors (GABAARs)
Authors: Turner Sara Marie , Johnson Stephen M
Published: June 2021

Progesterone and allopregnanolone (ALLO) are increased centrally during late pregnancy. Increased ALLO creates a risk for excessive neuronal inhibition because ALLO is a positive allosteric modulator of GABAARs. We hypothesized that XII motoneurons compensate for increased inhibition during late pregnancy by increasing epsilon subunit expression in GABAARs because the epsilon subunit confers insensitivity to positive allosteric modulators, such as ALLO and pentobarbital. To test this question, medullary slices were taken from G18 pregnant rats (n=7), adult male (n=5), and adult female (n=2) rats. Extracellular multichannel electrodes recorded spontaneous action potentials in XII motoneurons. To pharmacologically test for epsilon subunits, slices were sequentially exposed to 200 and 300 μM pentobarbital (45 min each). During the last 15 min of 300 μM pentobarbital, XII motoneuron firing rates steadily decreased to 37±9% (n=105 cells) and 36±5% (n=32 cells) of baseline in slices from male and female rats, respectively. In contrast, XII motoneuron firing rates from G18 rat slices increased to 120±29% of baseline (n=78 cells). These data show that pregnancy caused XII motoneurons to become more resistant to positive allosteric modulation by pentobarbital. We speculate that increased epsilon expression prevents excessive ALLO‐dependent inhibition during pregnancy. Supported by NIH T32 HL07654.
Dietary supplementation of Lessertia frutescens (Sutherlandia) enhanced host defense against Listeria monocytogenes in BALB/c mice
Authors: Lu Chi-Hua , Lei Wei , Browning Jimmy D , Eichen Peggy Ann , Fritsche Kevin L
Published: June 2021

Introduction

Sutherlandia (SU) is a South African botanical that has been widely used in treatments of cancer, HIV and infections. The goal of this study was to examine the impact of dietary supplementation of SU using a Listeriosis model.

Methods

BALB/c mice (n=72) were fed for 4 weeks one of the AIN93G diets containing 0%, 0.25% and 1% (w/w) dried and ground SU leaves and stems. Three day prior to sacrifice, mice were challenged i.v. with live Listeria monocytogenes (4×104 cfu for bacterial clearance, 5×106 cfu for cytokine/chemokine). The bacteria loads in spleen and liver, and 24 cytokines and chemokines in sera were measured.

Results

The bacteria loads in spleens averaged 2.2×107 (0%), 2×107 (0.25%), and 1.3×107 (1%) cfu/g. The bacteria load of the 1% treatment group was significantly lowered compared with control (p<0.06). For livers, the bacteria loads are averaged 5.2×103 (0%), 1.1×104 (0.25%), and 4.2×103 (1%) cfu/g. The bacteria load of the 1% treatment group was significantly lowered compared with 0.25% treatment group (p<0.05). Among 24 cytokines and chemokines, including: IFN‐gamma, IL‐1, IL‐6, TNF‐alpha, MCP‐1, IP10, significant differences were not observed among dietary treatment groups.

Conclusion

Dietary Sutherlandia modestly enhanced bacterial clearance of Listeria monocytogenes from spleen without affecting the production of cytokines and chemokines assayed.

Grant Funding Source: NIH P50 AT006273‐01
Whole‐grain foods and gastrointestinal and immune health in adolescents: A randomized intervention
Authors: Langkamp-Henken Bobbi , Nieves Carmelo , Girard Stephanie-Anne , Hughes Christine , Christman Mary C , Dahl Wendy J , Mai Volker , Boileau Thomas , Jonnalagadda Satya , Thielecke Frank
Published: June 2021

Intake of whole‐grain (WG) foods by adolescents is reported to be 1 oz eq or one‐third the recommended intake of 48 g/d. This study determined the effect of providing refined‐grain (RG, n=42) or WG (n=41) foods on gastrointestinal (GI) and immune health in adolescents (12.7±0.1 y). Students were recruited from a local middle school and randomized to receive RG or WG foods for 6 wk. Grain‐based foods (e.g., bread, cereals, snacks) were delivered weekly to subjects and their families. Two baseline and 6 weekly intervention dietary recalls were obtained. Stool output was recorded daily. Blood was drawn at baseline and final visits for immune markers. Across groups, total grain intake increased by 1 oz eq during the intervention. Intake of WG was similar at baseline (18±3 g) between groups but increased to 60±5 g and decreased to 4±1 g in the WG and RG groups. Number of daily stools increased by 0.0034 (P=0.08) per g WG, or an average of 0.2 stools/d increase for the WG group. LPS‐stimulated peripheral blood mononuclear cell production of TNF‐α, IL‐1β, and IL‐6 decreased and serum antioxidant concentrations increased from baseline in both groups (P<0.01) with no differences between groups. These data suggest that dietary changes associated with increased grain intake in general may affect inflammatory processes and WG in particular may impact GI function in adolescents. Support: General Mills Bell Institute of Health and Nutrition
Chronic hypoxia decreases fasting glucose and improves glucose tolerance in obese rats
Authors: Villafuerte Francisco Carlos , Macarlupu Jose Luis , Rojas Percy , Anza Cecilia , Gamboa Jorge Luis
Published: June 2021

People living at high‐altitude have lower fasting glucose levels and apparently lower incidence of type 2 diabetes. In lean mice, 4 weeks of hypoxia also decreases glucose levels and increases insulin sensitivity in skeletal muscle. However, the effect of chronic hypoxia on glucose metabolism and insulin sensitivity in obese and glucose intolerant rodents is unknown. We hypothesized that chronic hypoxia decreases fasting glucose level and improves glucose tolerance in obese rats. In order to test this hypothesis, Sprague‐Dawley rats were fed with normal chow diet or high‐fat diet (45% Kcal from fat) for 24 weeks in a normoxic environment. Rats were then exposed to hypobaric hypoxia(simulated altitude of 4500m)for 3 weeks. Fasting glucose (6h) and glucose tolerance test were measured before and after the hypoxic exposure. Chronic hypoxia reduces fasting glucose in both groups:37% decrease in lean rats (from 107.8±6.1 to 68.4±11.5, p<0.001) and 32.9% decrease in obese rats (from 111.8±13.9 to 75.0±13.6, p<0.001). Glucose tolerance curve shifts downward in both groups (lean and obese) after chronic hypoxia (figure). This result suggests that chronic hypoxia not only increases glucose utilization in lean but also in obese rodents. Further studies are required to evaluate the effects of chronic hypoxia on insulin sensitivity in obesity.

Supported by a grant from FINCyT (No 046‐FINCyT‐PITEI‐ 2010).
Heparan sulfate 6‐O‐sulfation is dynamically regulated in idiopathic pulmonary fibrosis
Authors: Lu Jingning , Lasky Joseph A , Yue Xinping
Published: June 2021

A glyco‐gene array approach was used to identify glyco‐genes involved in the development of idiopathic pulmonary fibrosis (IPF) with an emphasis on heparan sulfate (HS) biosynthesis and modification. Glyco‐gene expression profile (GlycoV4 oligonucleotide array) of normal and IPF human lungs identified 162 differentially expressed transcripts. Genes involved in HS biosynthesis and modification that were altered in IPF include HS N‐deacetylase/N‐sulfotransferase 1, HS 2‐O‐sulfotransferase, HS 6‐O‐sulfotransferases (HS6ST‐1 and ‐2), and HS 6‐O‐endosulfatases Sulf1 and Sulf2. The upregulation of both HS6STs and the Sulfs is intriguing as HS6STs add sulfates to the 6‐O‐position during HS biosynthesis, whereas the Sulfs remove them outside the cells. Quantitative RT‐PCR confirmed the upregulation of Sulf1, Sulf2 and HS6ST‐2. The overexpressed HS6ST‐2 was further identified as the HS6ST‐2S splice variant. Immunohistochemistry revealed that Sulf1 and Sulf2 were expressed in the fibrotic region and the hyperplastic type II alveolar epithelial cells, respectively, whereas HS6ST‐2S was localized in both epithelial and mesenchymal cells. Finally, HPLC analysis revealed that HS from IPF lungs were more 6‐O‐sulfated than that from normal lungs. In conclusion, HS 6‐O‐sulfation is dynamically regulated in IPF, and may play important roles in the development of IPF. This work was supported by NIH R03HL096949.
Membrane trafficking produces distinct beta‐adrenergic signaling for Cl secretion and K secretion in guinea pig distal colonic mucosa
Authors: Halm Susan , Zhang Jin , Halm Dan
Published: June 2021

Epinephrine (epi) activated Cl and K secretion (sec) in isolated mucosa from guinea pig distal colon, measured as short‐circuit current. These components of the response were distinguished by inhibition of Cl sec with a β2 antagonist (ICI‐118551) that spared K sec; propranolol inhibited both. Interfering with endocytosis prolonged the transient Cl sec and inhibited sustained K sec. Both the dynamin inhibitor dynasore and the clathrin‐coated‐pit blocker mono‐dansylcadaverine produced this response. Dynasore also inhibited the sustained epi‐induced increase in mucosal cAMP, while leaving the transient cAMP increase intact. Manipulating the ubiquitylation cycle by inhibiting ubiquitin‐E1 ligase (UBEI‐41, BioGenova) also prolonged the epi‐induced Cl sec transient and slowed the onset of K sec. Conversely, inhibiting deubiquitylases (PR‐619, LifeSensors) alone stimulated K sec, while blunting Cl sec and producing a non‐additive increase in K sec with epi. Disruption of the actin (latrunculin B, cytochalasin D) and microtubule (nocodazole) cytoskeleton inhibited epi‐induced K sec without altering Cl sec. Together these results support an activation process involving internalization of β2‐adrenergic receptors that terminates signaling for Cl sec, and β‐adrenergic stimulation of K sec that requires receptor internalization prior to activation of the sustained cAMP signaling cascades. [NIH DK65845]
An Association between Type Igamma PtIns4P 5‐Kinase and Exo70 Directs E‐cadherin Clustering and Epithelial Polarization
Authors: Xiong Xunhao , Xu Qingwen , Huang Yan , Singh Raman Deep , Anderson Richard , Leof Edward , Hu Jinghua , Ling Kun
Published: June 2021

The mechanisms underlying E‐cadherin clustering and AJ maturation are not fully understood although the E‐cadherin‐mediated formation of adherens junctions (AJs) is essential for the morphogenesis of epithelial cells. Here we report that the association between type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) and Exo70 regulated the transport and clustering of Ecadherin on the plasma membrane and, subsequently, the extension of nascent E‐cadherin adhesions. We also observed that PI4,5P(2) accumulation at E‐cadherin clusters during the assembly of E‐cadherin adhesions. PIPKIγ‐generated PI4,5P(2) is required for recruiting Exo70 to newly formed E‐cadherin junctions and facilitates the assembly and maturation of AJs. Additionally, Rho activity and actin structure were impaired by loss of Exo70 and/or PIPKIγ. These results support a model in which PIPKIγ and PIPKIγ‐generated PI4,5P(2) pools at nascent E‐cadherin contacts cue Exo70 targeting and orients the tethering of exocyst‐associated E‐cadherin. This could be an important mechanism that regulates E‐cadherin clustering and AJ maturation, and actin reorganization, which is essential for the establishment of solid, polarized epithelial structures.
Interaction of NKCC2 With SNARE Proteins in the Thick Ascending Limb
Authors: Caceres Paulo Sebastian , Ortiz Pablo Alfredo
Published: June 2021

NaCl absorption by the apical Na/K/2 Cl cotransporter (NKCC2) in thick ascending limbs (TAL) is important for blood pressure regulation and urinary concentration. NKCC2 levels in the apical membrane are maintained via exocytic insertion and endocytic retrieval. Inserted NKCC2 may derive from a newly synthesized pool or from those retrieved and then recycled. These processes are called trafficking, and involve several fusion events. Vesicle fusion is mediated by SNARE proteins from the VAMP, SNAP and syntaxin families. NKCC2 may directly interact with these proteins during trafficking into the apical membrane. We showed that VAMP2 and 3 are involved in NKCC2 trafficking in TALs. We hypothesized that NKCC2 directly interacts with VAMP 2, 3, and other SNAREs in TALs. We first studied SNARE expression and localization. We found that TALs express VAMP 2 and 3, SNAP 23 and syntaxins 3 and 4. VAMP 2 and 3, syntaxin 3 and SNAP 23 were localized to the apical membrane and subapical space similar to NKCC2. Syntaxin 4 was distributed throughout the cell. Next we performed co‐immunoprecipitation studies study protein interactions. VAMP 2 and 3 co‐immunoprecipitated with NKCC2 but the other SNAREs did not. Antibody specificity was tested with peptides and brain lysates. We conclude that NKCC2 interacts with VAMP 2 and 3 in TALs. SNAP23 and syntaxin 3 may be involved in NKCC2 trafficking without directly binding NKCC2. Funding: NIH, AHA
Characterization of Bile Acid homeostasis in Germ‐free Mice
Authors: Selwyn Felcy , Klaassen Curtis D
Published: June 2021

Gut bacteria metabolize primary bile acids (BAs) in bile, to form secondary BAs. Changes in gut bacteria will alter BA composition in the host. The purpose of this study was to characterize BA composition in mice lacking the normal complement of bacteria. BA concentrations in sera, livers, gallbladder bile, and ileal tissue of conventional (Conv) and germ‐free (GF) mice (3‐months old, n=5/group) were quantified using a UPLC‐MS‐MS method. The mRNA of BA synthetic enzymes in liver was quantified by bDNA assays. The GF mice have increased total BAs in liver (3‐fold), gallbladder (40‐fold), and ileum (4‐fold). Taurine (T)‐conjugated BAs increased in serum, gallbladder bile, and ilea of GF mice. T‐conjugated β‐muricholic acid (βMCA) was the predominant BA in livers of GF mice, whereas T‐cholic acid was the predominant BA in livers of Conv mice. The mRNA of enzymes belonging to the alternative pathway for the synthesis of βMCA namely, Cyp27a1 and Cyp7b1 were increased in GF mice liver. T‐UDCA, which is thought to be a secondary BA, was increased in liver (3‐fold), ileum (3‐fold) and gallbladder (35 fold) of GF mice, suggesting that UDCA may be a primary BA in mice. In summary, this study suggests: (1) GF mice favor the synthesis of βMCA in the liver; (2) BA concentrations are increased in livers, gallbladders, and ileal tissue of GF mice, and (3) UDCA appears to be a primary BA. (Supported by grants DK‐081461, ES‐019487 and ES‐009649)
Inhibition of chloride secretion by capsaicin in T84 cells is independent of the transient receptor potential vanilloid type 1
Authors: Bouyer Patrice G. , Tang Xu , Weber Christopher R , Shen Le , Turner Jerold R , Matthews Jeffrey B
Published: June 2021

Capsaicin is a known agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1), which is expressed in various epithelial cells and whose role remains elusive. Infusion of capsaicin was reported to block chloride secretion in the rat colon. We tested whether capsaicin blocks chloride secretion directly by acting on the epithelial cells. In mouse colon and T84 cells capsaicin blocked the forskolin‐stimulated short‐circuit current (FSK‐Isc). The presence of TRPV1 in colonic epithelial cells was shown by western blotting. In T84 cells, TRPV1 localized at the basolateral membrane and in vesicular compartments in the cell. Capsaicin treatment induced endocytosis of the Na‐K‐Cl‐cotransporter 1 (NKCC1) demonstrated by immunocytochemistry and basolateral surface biotinylation. AMG‐9810 an inhibitor of TRPV1 did not prevent the inhibition of the FSK‐Isc by capsaicin. Capsazepine another TRPV1 antagonist mimicked the effect of capsaicin. Finally, neither resiniferatoxin nor N‐Oleoyldopamine, two selective agonists of TRPV1, blocked the FSK‐Isc. In conclusion, capsaicin inhibits chloride secretion in T84 cells in part by causing NKCC1 internalization via a TRPV1‐independent mechanism.
The Effect of Dietary Pulses on Lipids in Controlled Feeding Trials: A Systematic Review and Meta‐Analysis
Authors: Ha Vanessa , de Souza Russell J , Sievenpiper John L , Jayalath Viranda H , Beyene Joseph , Jenkins David JA , Kendall Cyril WC
Published: June 2021

Background

Although there is evidence from controlled feeding trials that dietary pulses (beans, peas, chickpeas, and lentils) may benefit lipid control, cardiovascular guidelines have not addressed dietary pulses in their recommendations.

Aim

A systematic review and meta‐analysis was conducted to assess the effect of dietary pulses on established therapeutic lipid targets for cardiovascular risk reduction.

Methods

We searched MEDLINE, EMBASE, Cochrane, and CINAHL databases through June 13 2011 and included human trials of at least 3 weeks in duration. Data were pooled by the generic inverse variance method using random effects models and expressed as mean differences (MD) with 95% confidence intervals. Heterogeneity was assessed (Chi2) and quantified (I2). Study quality was assessed using the Heyland Methodological Quality Score (MQS).

Results

24 isocaloric trials (n= 808) met the inclusion criteria. Diets supplemented with dietary pulses significantly lowered LDL‐C levels (MD= −0.22 [95% CI: −0.32, −0.12]) and non‐HDL‐C (MD= −0.24 [95% CI: −0.37, −0.11]) compared with isocaloric control diets. No significant effects were observed for TC:HDL, ApoB, and ApoB:ApoA.

Limitation

The majority of trials were of low quality.

Conclusions

Pooled analyses demonstrated that dietary pulses significantly improved LDL‐C and non‐HDL levels.

Funding: Pulse Canada, Saskatchewan Pulse Growers

Grant Funding Source : ASN
The cytosolic branched‐chain aminotransferase (BCATc) regulates T cell activation via mTOR signaling pathway
Authors: Ananieva Elitsa A , Patel Chirag , Powell Jonathan , Hutson Susan
Published: June 2021

The mammalian target of rapamycin (mTOR) integrates environmental cues such as amino acids and growth factors to direct T cell activation and differentiation. T cells have unique metabolic demands to support their own differentiation into subsets with specific functions to promote or suppress immunity. Here we describe a new candidate for an immunosupressive enzyme, the cytosolic branched‐chain aminotransferase (BCATc), which impacts mTOR signaling in T cells. BCATc is a metabolic enzyme that catalyzes the first step in leucine, isoleucine and valine degradation. BCATc protein levels and activity are 15‐ and 13‐fold higher under anergy, an immunological condition known as absence of an immune response. Under anergic conditions, T cells isolated from BCATc−/− mice had an up‐regulated mTOR signaling compared to anergic T cells isolated from wildtype mice. Phosphorylation of the mTOR substrates, S6 and 4EBP‐1, were 3.9 and 4.9 fold higher than in wildtype mice. The results suggest that BCATc or changes in BCAA metabolites may inhibit mTOR signaling under anergy and that lack of BCATc enzyme reverses the inhibition, possibly triggering T cells to full activation. Understanding the role of BCATc in T cell immunity will provide new strategies for nutritional therapy in modulating the immune response to promote treatment of autoimmune diseases or develop anti‐tumor vaccines. (Support: R01DK 34738 & Virginia Tech).
Excess pregnancy weight gain and early energy‐rich environment in swine program offspring for indications of metabolic syndrome
Authors: Arentson Emily J , Potu Ramesh , Ragland Darryl , Buhman Kimberly K , Ajuwon Kolapo , Donkin Shawn S
Published: June 2021

Many pregnancies in the United States result in weight gain in excess of recommendations. Few data exist on the impact of maternal weight gain on offspring despite evidence demonstrating that early life environment precipitates risks for metabolic syndrome. Excessive gestation weight gain and postnatal diet were assessed using a swine model of human health. Offspring from Landrace x Duroc gilts fed a normal (mNE) or a high energy diet (mHE) to induce a 30% increase in gestation weight gain were weaned to either a normal (wNE) or high energy (wHE) diet. At 3 months of age piglets fed wHE had increased (P < 0.05) backfat compared with wNE and suppressed (P < 0.05) hepatic and intestine (1.51 vs. 0.48 and 0.85 vs. 0.47, respectively for wNE vs. wHE) PEPCK‐C abundance. Intestine PGC‐1α abundance was significantly lower in offspring from mHE gilts (0.94 vs. 0.60 for mNE vs. mHE). Offspring from mHE gilts weaned onto a wHE diet had elevated (P < 0.05) blood glucose (102 vs. 64 mg/dl), insulin (0.10 vs. 0.21 ng/ml) and lower NEFAs (0.62 vs. 0.31 mmol/L) compared to mHEwNE offspring. Postnatal wHE did not induce the same metabolic perturbations in the mNE offspring (GLU 70 vs. 80 mg/dl, ILN 0.16 vs. 0.13 mg/dl, NEFA 0.43 vs. 0.43 mmol/L for mNEwNE vs. mNEwHE). These data show gestational weight gain of 30% in excess of recommendations and a nutrient‐rich postnatal environment precipitate indications of metabolic syndrome.

Grant Funding Source : Showalter Trust Fund
Concordance with the WHO guidelines for early child feeding through the first six months of life in a sample of infants of the Guatemalan highlands
Authors: van Beusekom Ilse , Vossenaar Marieke , Montenegro-Bethancourt Gabriela , Doak Colleen M , Solomons Noel W
Published: June 2021

Background

The WHO recommends exclusive breastfeeding (EBF) through the first 6 mo of life. EBF is defined as having received only breast milk during the previous day. Predominant breast feeding (PBF) allows the infant to receive certain liquids such as water, juices and ritual fluids.

Objective

To evaluate EBF and PBF rates in a sample of infants from a low‐income, urban Guatemalan population using 3 different interview methods.

Methods

Mothers of 154 infants (77 boys) in their 6th mo of life, attending a public health center, were recruited and interviewed on a single occasion regarding previous day (as suggested by the WHO), current, and past (since birth) feeding practices.

Results

Using the previous day recall, EBF was reported by 86 (56%) of the mothers. Estimated EBF rates were much lower when based on current feeding practice questions (20%) and even lower when based on feeding practices since birth (9%). Using the less stringent recommendation allowing certain liquids, we observed PBF rates of 58%, 49% and 31% based on previous day, current and past reported feeding practices, respectively.

Conclusion

The WHO method overestimates the EBF rate compared to the recall since birth. Overall, adherence to the WHO guidelines for feeding in the first semester of infancy was much less than ideal and in need of strengthening.

Funded by the Nestlé Foundation, Switzerland
Secular trends in female adult stature in relationship to gross domestic product around time of birth
Authors: Self Julie Lynn , Stein Aryeh D.
Published: June 2021

Average adult height is a commonly used indicator of biological standard of living. The secular increases in height observed for many developed countries are believed to result from improved health and nutrition in early childhood. Evidence from developing countries is less thorough and consistent. We characterized the relationship between secular trends in adult female height and real gross domestic product per capita (GDP) at the time of the woman's birth by country and region using Demographic and Health Survey data and World Bank estimates. The overall change in adult height in women born between 1945 and 1980 was 0.77 cm. Average slopes differed (t=7.0, p<0.001) between 23 African countries (−0.004 cm/year) and 17 other countries (0.062 cm/year). African countries also differed from non‐African countries in the relationship between adult height and GDP in early life. The relationship was nonsignificant for African countries (coefficient=−0.39 cm/lnGDP, p=0.3), but significantly positive for non‐African countries (coefficient=1.59 cm/lnGDP, p<0.001). The relationship between adult female height and economic conditions is inconsistent and modified by other factors in the developing world context.
INHIBITION OF NOX1 OXIDASE EXACERBATES INFLUENZA A VIRUS‐INDUCED LUNG INFLAMMATION
Authors: Selemidis Stavros , Seow Huei Juinn , Broughton Brad , Bozinovski Steven , Vinh Antony , Stambas John , Sobey Christopher , Drummond Grant , Vlahos Ross
Published: June 2021

The Nox2 isoform of the NADPH oxidase family of superoxide‐generating enzymes promotes the lung injury and inflammation to influenza A virus infection. However, airway epithelial cells and lung endothelial cells also express the Nox1 isoform of NADPH oxidase placing this enzyme at key sites to regulate influenza A virus‐induced lung inflammation. Male WT and Nox1‐deficient mice (Nox1−/y) were infected with 1×104 PFU of the moderately virulent influenza A virus HKx31 (H3N2) and sacrificed 3 and 7 days post infection. HKx31 virus infection of Nox1−/y mice resulted in significantly greater: loss of bodyweight; BALF neutrophilia; peri‐bronchial, peri‐vascular and alveolar inflammation; BALF inflammatory cell superoxide production and peribronchial, epithelial and endothelial oxidative stress; and expression of pro‐inflammatory cytokines including CCl2, CCl3, CXCl2, IL‐1β, IL‐6 and TNF‐α when compared to WT mice. Expression of the anti‐inflammatory cytokine IL‐10 was lower in Nox1−/y mice. Lung viral titers and airways infiltration of active (i.e. CD69+ and CD44+) CD8+ and CD4+ T lymphocytes, and of Tregs (CD25+CD4+FoxP3+) were similar between influenza‐infected WT and Nox1−/y mice. These data indicate that Nox1 oxidase protects against influenza A virus infection in mice and that there are differential roles of Nox1 versus Nox2 oxidases in the regulation of inflammation caused by influenza A viruses.
Glutamine Synthetase plays a dual role in the dependence of human cancer cells from glutamine
Authors: Chiu Martina , Tardito Saverio , Gazzola Renata Franchi , Bianchi Massimiliano G. , Uggeri Jacopo , Bussolati Ovidio
Published: June 2021

GS‐positive and GS‐negative human cancer cells were compared to study the relationships between Glutamine Synthetase (GS) and the sensitivity to Gln depletion. Gln depletion was obtained with either Gln withdrawal or L‐asparaginase treatment. β‐Catenin‐mutated human Hepatocellular Carcinoma (HCC) HepG2 cells highly expressed GS mRNA under control conditions (4 mM extracellular Gln) and exhibited increased GS protein and activity upon Gln depletion. Compared with β‐catenin wild type Huh‐7 cells, HepG2 cells had higher intracellular levels of Gln under control conditions but were more sensitive to Gln starvation, thus exhibiting features of Gln addiction. Two oligodendroglioma cell lines, Hs683 and HOG, failed to express GS protein even upon prolonged asparaginase treatment but were much more sensitive to Gln starvation than GS‐positive U87 glioblastoma cells. Upon Gln starvation, GS inhibitors synergized cytotoxicity in GS‐positive HCC and glioblastoma cells, but were without effect in GS negative oligodendroglioma cells. Thus, under conditions of Gln shortage the adaptive increase of GS protein is a pro‐survival factor, while GS overexpression in Gln‐fed cells may be a marker of Gln addiction.
Neural stem cells: From basic biology to tissue repair
Authors: Morshead Cindi
Published: June 2021

The isolation and characterization of neural stem cells in the adult brain offers considerable hope for the treatment of CNS injury and disease. I will discuss the fundamental biology of neural stem and progenitor cells in the adult brain and our work to date using small molecules to activate these endogenous neural precursor cells to effectively enhance “self‐repair” of the stroke injured brain.
Trends in Histology and Embryology – Survey Results from North American Dental Course Directors
Authors: Lee Lisa M.J. , Burk Dorothy T , Lambert H. Wayne
Published: June 2021

As a part of the Basic Science Survey Series, members of the American Dental Education Association Anatomical Sciences Section performed a survey to assess how embryology and histology are taught to dental students across North America. The purpose of this study was to examine current trends in embryology and histology education with respect to course content, teaching methods, and other pertinent information that will serve as a useful guideline in many aspects of dental education and curriculum reform. 97 faculty members representing 60 North American dental schools participated in the survey (89.6% response rate). The results of the survey reveal amongst other things, the following trends: 1) heavy reliance on medical school faculty for embryology and histology education; 2) aging population of embryology and histology instructors; 3) increase in curricular change with a pattern of decreasing basic science curricular hours and increasing integration and clinical emphasis; 4) increase in computer‐assisted instruction; 5) histology is taught with lab experience in most institutions but only a few programs offer an embryology lab; 6) there are common histology and embryology content items emphasized. The results will be of value for dental faculty, administrators and board exam construction committees in making informed decisions on program evaluation, future curricular change and assessment criteria.
Selenoprotein P (Sepp1) Synthesis by the Liver Protects against Selenium Deficiency
Authors: Hill Kristina E. , Motley Amy K. , Atkins John F. , Capecchi Mario R. , Wu Sen , Burk Raymond F.
Published: June 2021

Sepp1 is a widely expressed selenium‐rich plasma protein taken up for its selenium by testis, brain, and other tissues. The role of Sepp1 in transport of selenium from liver to peripheral tissues was studied in mice with selective deletion of Sepp1 in the liver (Sepp1fl/fl x Alb‐cre mice). Sepp1fl/fl x Alb‐cre mice and Sepp1fl/fl controls were fed semi‐purified diets with defined selenium content. Sepp1fl/fl x Alb‐cre mice fed diet supplemented with 0.25 mg selenium/kg had 4% Sepp1, 13% glutathione peroxidase activity, and 9% selenium in plasma when compared with controls. The selenium concentrations of kidney, muscle, and whole body were depressed, but liver, brain, and testis retained selenium relatively well. When fed selenium‐deficient diet for 26 weeks, Sepp1fl/fl x Alb‐cre mice lost strength in their hind legs. They pulled in their legs when lifted by the tail in contrast to the splaying of legs by controls. Their weight diverged downward from controls fed the same diet beginning at 16 weeks on diet. Thus, Sepp1fl/fl x Alb‐cre mice have low plasma Sepp1 but enough Sepp1 to supply brain and testis with selenium. When fed selenium‐deficient diet, however, Sepp1fl/fl x Alb‐cre mice become selenium deficient before control mice, reflecting selenium wasting in the urine that occurs when Sepp1 synthesis does not compete with excretory metabolite production in the liver. Supported by NIH ES02497.
Leucine modulation of sirtuins and AMPK in adipocytes and myotubes
Authors: Liang Chunzi , Bruckbauer Antje , Zemel Michael B
Published: June 2021

Previous data from this lab demonstrates that leucine stimulates Sirt1 expression and activity, as well as downstream mitochondrial biogenesis and fatty acid oxidation in myotubes. We have now investigated the effects of leucine and its metabolites on both Sirt1, mitochondrial Sirt3 and AMP‐activated protein kinase (AMPK) in 3T3‐L1adipocytes. Leucine (0.5 mM) stimulated Sirt1 expression ~2‐fold (p=0.009) but not activity, while it's metabolites (α‐keto isocaproic acid [KIC] and β‐hydroxy‐β‐methyl butyrate [HMB]) exerted little effect; neither valine nor alanine (controls) exerted any effect. In contrast, leucine exerted little effect on Sirt3 expression, while both leucine and HMB (50 μM) increased Sirt3 activity (p=0.006); this was associated with a marked increase in P‐AMPK protein expression. Both leucine and HMB, but not KIC, stimulated ~2‐fold increase in PGC1α expression (p=0.004). In C2C12 myotubes, leucine and HMB both stimulated Sirt1, Sirt3 and AMPK activity (p<0.01). To mimic the effects of fasting and feeding, myotubes were exposed to reduced (5.5 mM) and high (11.1 mM) glucose; leucine stimulated Sirt1 under both conditions (p=0.003), but increasing glucose decreased Sirt1 under basal conditions and blunted the response to leucine. These data suggest that sirtuins, AMPK and downstream signals are sensitive to leucine in adipocytes as well as myotubes.

Grant Funding Source: Nutraceutical Discoveries, Inc.
Dietary wolfberry increases hepatic insulin sensitivity in obese mice
Authors: Lin Dingbo , Jiang Yu , Wark Logan , He Hui , Willard Lloyd , Medeiros Denis
Published: June 2021

Objective

To determine whether dietary wolfberry reverses insulin resistance in obese mice.

Methods

Male C57BL/6J mice, at 6 weeks of age, were divided into 3 groups, 15 mice for each group, for a 28‐week dietary study. Three different diets were 10 kcal % fat diets as a low fat diet control, 45 kcal % fat diets (high fat diet), and high fat diets with 1 % (kcal/kcal) wolfberry fruits. Food consumption, body weight and fasting blood glucose were monitored weekly. At termination of study, 6 mice from each group were subjected to test of oral glucose tolerance and insulin resistance. The rest mice were euthanized for biochemical analysis. Liver oxidative stress was determined by production of reactive oxygen species (ROS). Uncoupling protein UCP2, ER stress biomarkers, IRS‐1 and IRS‐2, AKT, and acetyl‐CoA carboxylase (ACC) were determined by Western blotting.

Results

Mice fed high fat diets developed obesity, hyperlipidemia, and hepatic steatosis. High fat diets induced elevation of ROS levels, decreases of UCP2, activation of ACC and ER stress. Dietary wolfberry attenuated oxidative stress and ER stress, and increased insulin sensitivity. However, hepatic steatosis was not altered.

Conclusions

Wolfberry at 1 % (kcal/kcal) increases hepatic insulin sensitivity in obese mice most likely through attenuating cellular oxidative stress and subsequent ER stress. Hepatic insulin resistance is independent of steatosis. Grant Funding Source: National Institutes of Health COBRE Grant P20‐RR‐017686
Prenatal effects of selenium and isoflavones in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice
Authors: Nakken Heather Lindsay , Mcleod Kelly A , Rasmussen Julie K , Randall Tyler J , Churchill Deverall , Christensen Merrill J
Published: June 2021

Effects of supplemental selenium (Se) may depend on the timing of their addition (Tolman 2008) and the composition of the basal diet to which they are added (Quiner 2011). We fed female FVB mice stock diets high or low in isoflavones, with or without a supplement of Se (4.0 mg Se/kg body weight as Se‐methylselenocysteine) by gavage 5 days a week. After 30 days, females were mated with homozygous TRAMP C57BL/6 males. Females continued their dietary treatments through pregnancy and lactation. Pups were weaned at 21 d to the same dietary treatments as their dams and were sacrificed at 4 wk. High isoflavone intake and Se supplementation each decreased body weight, urogenital tract weights (%BW), expression of SV40 large T antigen (which drives tumorigenesis in TRAMP) in dorsolateral (DLP) and ventral prostate (VP), and expression of synaptophysin (VP) (a marker of neuroendocrine tissue). For body weight, urogenital weight, and large T expression (VP), the combination of high isoflavones and Se supplementation resulted in greater decreases than those produced by either factor individually. Interestingly, expression of the androgen receptor was increased by high isoflavones and by Se supplementation in DLP, but only by high isoflavones in VP. These data suggest that cancer progression in this model may be affected by prenatal exposure to supplemental Se and/or high isoflavones. Supported by NIH CA141385 to MJC.
Protective effects of berries and walnuts against the accelerated aging and age‐associated stress caused by irradiation in critical regions of rat brain
Authors: Poulose Shibu M , Bielinski Donna F , Gomes Stacey M , Carrihill-Knoll Kirsty , Rabin Bernard M , Shukitt-Hale Barbara
Published: June 2021

The occurrence of neurodegenerative disease substantially increases with age, which, in part, may be due to increased susceptibility to oxidative stress, inflammation and loss of autophagy (neuronal housekeeping). Polyphenols and ω‐fatty acids, abundant in berries (e.g., blueberry, strawberry, or acai fruit) and walnuts, have been shown to protect brain cells in culture and animals against oxidative stress/inflammation, with enhanced memory and cognitive function in animals. We have investigated whether feeding rats with blueberry‐ or strawberry‐supplemented diets, followed by irradiation with high energy and charge (HZE) particles, a model for accelerated aging, would elicit any protective effects in the brain. HZE irradiation disrupted key proteins in the hippocampus and striatum. Feeding animals with either berry diet, prior to irradiation, protected these brain regions against inflammation, oxidative stress and loss of autophagy. Moreover, autophagy activation was mediated by inhibiting the phosphorylation of mTOR and activating other proteins. Walnuts also elicited similar effects on the normal aging process when fed to aged animals. These molecular effects were further corroborated in vitro using BV2 microglia, HT22 neurons and E18 neuron‐astrocyte cultures. This study extends molecular evidences for the health‐promoting properties of berries and walnuts.

Grant Funding Source: USDA intramural grant
Dietary supplement (DS) use of children <18 yr in the 2007 National Health Interview Survey (NHIS)
Authors: Dwyer Johanna T , Bailey Regan , Nahin Richard , Rogers Gail , Sempos Christopher , Jacques Paul
Published: June 2021

The NHIS offers unique information on DS use in parent‐child pairs, including information on perceived health and other characteristics not obtained by other national health surveys. In NHIS 37% of children used DS (n=9227). Child use was lower than parent use but similar by type of DS. Users differed from nonusers in socio‐demographics (Asian, White, Non‐Hispanic race/ethnicity, region of residence, higher family parental education and income, private health insurance, usual place of receiving conventional medical care) and proxy reported health status (“good/very good/excellent” health), rare doctor visits & hospitalizations. Children received DS for prevention or treatment of many illnesses & conditions. Neither reasons nor specific types of DS were associated with particular conditions. NHIS data can be used to describe DS use in a much different way than that of NHANES. The strengths and limitations of both surveys for addressing DS use will be discussed. Funding: ODS/NIH; NCCAM/NIH; and USDA HNRCA/Tufts.
Increase in physical activity among Central Brooklyn residents participating in an incentive‐based walking program
Authors: Hoy-Rosas Jamillah , Klein Brett
Published: June 2021

Intro

The “Brooklyn‐Stay Well, Enjoy Life” (B‐SWEL) program is a grant funded initiative sponsored by the Office of Minority Health that will provide 1,200 Central Brooklyn residents with screening, education, and diabetes prevention services over 3 years. B‐SWEL aims to help pre‐diabetics avoid disease progression and diabetics successfully manage their illness. Clients receive individual case management and group services to help them achieve weight loss, reduce blood pressure and control blood sugar.

Methods

B‐SWEL participants enrolled in a 6‐month walking program. They received an accelerometer that tracked their daily steps for 7 days. Participants were offered 3 occasions per week to participate in an hour‐long neighborhood group walk. Participants received cash incentives for achieving the highest number of steps per week and per month.

Results

20 participants enrolled. 95% of participants were Black, 65% were obese, 55% had high blood pressure, 20% were pre‐diabetic and 45% were diabetic. Average number of weekly steps of the participants at the onset of program was 60,291. After 1 month, the average number of weekly steps increased to 63,956.

Conclusion

Incentive‐based walking programs conducted in community‐based settings are an important way to increase physical activity among high‐risk populations.
The association between sugar intake and HDL levels varies by sugar type and source
Authors: Welsh Jean A. , Vos Miriam B.
Published: June 2021

Higher intake of added sugars has been associated with dyslipidemia and increased cardiovascular disease risk but little is known about the impact of consuming food and beverage sources of naturally occurring sugars. The purpose of our study was to determine if the association between dietary sugars and high‐density lipoprotein (HDL) levels vary by sugar type (naturally occurring vs. added) and source (foods vs. beverages) in U.S. adolescents (12–18 y; n=2918). We used dietary and blood lipid data from the National Health and Nutrition Examination Survey (NHANES), 2003–2006 and added sugar content data from the MyPyramid Equivalents Database version 2.0 (MPED). In linear regression models controlling for age, race, gender, BMI percentile, physical activity, total energy and fat intake, HDL levels were 0.12 mg/dL lower for each additional tsp. of added sugar consumed in beverage form (p=0.001). There was no association between HDL levels and the added sugar obtained in foods or between HDL and the naturally occurring sugars obtained in foods and beverages. While further research is needed to understand the lipid effect associated with dietary sugars, our results suggest that the consumption of sugar‐sweetened beverages may uniquely affect HDL levels.
X‐Ray fluorescence as an assay tool for musculoskeletal nutrition animal research
Authors: Branly Rolando M , Tulp Orien , Karam David
Published: June 2021

XRF techniques are well established for the measurement of the presence of lead and heavy metals in osseous tissue. The advent of compact pyroelectric crystal x‐ray generators and silicon drift detectors presents a new opportunity for nutrition research that studies muscular, vascular and epithelial tissue. We compare the measurable ratios of Fe/K, Fe/Ca, and Fe/Cl in different bovine muscle tissues to establish a baseline feasibility study in preparation for in‐vivo measurements. The low power and portability characteristics of new technology XRF systems make it possible to examine epithelial tissue characteristics of animals in‐vivo. Limited initial calculations and models with backscattered x‐rays utilizing non‐imaging optics indicate promise. Non‐imaging optics are used to increase the effective collecting area of the spectral detection system in the backscatter configuration. We propose the concept that strategically selected ion ratios in muscle and vascular tissues can aid in quantifying “nutritional health” in laboratory animals. We acknowledge institutional support.
Human milk oligosaccharides inhibit acute rotavirus infection in neonatal piglets
Authors: Hester Shelly N , Comstock Sarah S , Monaco Marcia H , Kuhlenschmidt Theresa B , Kuhlenschmidt Mark S , Donovan Sharon M
Published: June 2021

Human milk oligosaccharides (HMO) are being investigated as potential additives to infant formula. Herein, acute HMO treatment within the ileal lumen of both healthy and acutely rotavirus (RV)‐infected piglets was studied. Piglets (n=9 group) were fed formula from 48h to d21 of age. At d21, a midline laparotomy was performed and six 10cm loops of ileum were isolated in situ. The following treatments were injected into the loops: media, a single HMO, an HMO mixture (mHMO), or each treatment + OSU strain RV (1 × 107 FFU). After treatment, samples were collected. Loops treated with the single HMO + RV or with the HMO mixture + RV had lower RV replication, as assessed by NSP4 mRNA expression, than other RV‐treated loops (p=0.0026). Ileal loops not treated with RV showed no NSP4 expression. There was no difference in cytokine mRNA expression in ileal mucosa as analyzed by loop or dietary treatment. In conclusion, a single HMO or unique HMO mixture decreased NSP4 expression during acute RV infection. (Supported by Abbott Nutrition)
Genome‐wide combinatorial transcriptional regulatory dynamics during early onset of liver regeneration and chronic alcohol intake
Authors: PATRA BISWANATH , Kuttippurathu Lakshmi , HOEK JAN B , Vadigepalli Rajanikanth
Published: June 2021

The objective of this study is to characterize effects of chronic alcohol consumption on genome‐scale transcriptional regulatory network dynamics during the early phase liver regeneration after 70% partial hepatectomy (PHx) at 6h post 2/3rd PHx in the rat. Rats were fed liquid diet containing 36% of total calories derived from ethanol for 5 weeks, controls were pair‐fed an isocaloric liquid diet with carbohydrate replacing ethanol. Genome‐wide binding targets for NF‐kB, C/EBPbeta, and STAT3 were detected either by Roche NimbleGen ChIP‐chip or ABI SOLID sequencing approach. Our results indicate significant differences in the binding profiles of all the three regulators in chronic ethanol compared to isocaloric controls, at baseline as well as in response to PHx. Pathway analysis revealed that potential target genes specific to the chronic ethanol group participate in key processes such as mitochondria processing, DNA methylation, cell death, proteolysis, histone modification, lipid biosynthetic process, and regulation of cell cycle. Our results provide a first system‐wide view of the regulatory network dynamics in liver regeneration as it is affected by alcohol, and implicate combinatorial regulatory modules as participating in the adverse liver regeneration response. Research Support: NIH AA018873 and AA017261.