bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Endothelial and Skeletal Myofiber VEGF Gene Deletion Leads to Capillary Regression in Adult Mouse Hind Limb Muscle
Authors: Sulaeman Alexis Gabriella , Delavar Hamid , Fine Janelle , Wagner Peter D , Breen Ellen C
Published: June 2021

In adult mice, the importance of vascular endothelial growth factor (VEGF) for maintaining skeletal muscle capillaries is unclear. We hypothesized that deletion of the VEGF gene, targeted simultaneously to both endothelial cells and myofibers, would lead to a loss of capillaries in locomotor muscles.

Methods

Capillary to fiber ratio (C:F), fiber‐cross sectional area (FCSA), and fiber‐type composition were measured in soleus, plantaris and gastrocnemius cryo‐sections from wild type (WT) and HSA‐Cre‐ERT2 X VEGFLoxP x PDGFb‐iCre‐ERT2 (EC+MyoVEGF−/−) mice. C:F was decreased in soleus from EC+MyoVEGF−/− mice compared to WT (WT, 1.64 ± 0.19, EC+MyoVEGF−/− 1.20 ± 0.19, n=3–9, p < 0.05). FCSA increased in both EC+MyoVEGF−/− soleus and plantaris (soleus: WT, 1953 ± 347 μm2, EC+MyoVEGF−/−, 3148 ± 543 μm2, plantaris: WT, 1731 ± 189 μm2, EC+MyoVEGF−/−, 3261 ± 803 μm2, n=3–9, p < 0.05). EC+MyoVEGF−/− mice also revealed a shift from type IIB to type IIA fibers in the plantaris (type IIB: WT, 66 ± 7 %, EC+MyoVEGF−/−, 48 ± 8 %, type IIA: WT, 19 ± 4%, EC+MyoVEGF−/−, 36 ± 16%, n=3–9, p < 0.05). Unlike previously reported studies in adult skeletal myofiber VEGF‐deficient mice, capillary regression does occur in adult skeletal muscle when VEGF expression is inhibited in both endothelial cells and myofibers.
Rac1 is a novel regulator of stretch‐induced glucose uptake in muscle
Authors: Sylow Lykke , Kleinert Maximilian , Richter Erik A , Jensen Thomas E
Published: June 2021

Objective

The actin‐cytoskeleton‐regulating GTPase Rac1 is required for insulin‐stimulated glucose uptake in cultured muscle cells and is dysregulated in insulin resistant states. We previously found that both insulin and exercise activates Rac1 in mouse and human skeletal muscle, and is required for glucose uptake induced by these stimuli. However, it is unknown whether mechanical stress, which is an integrated component of muscle contraction and increases glucose uptake, activates Rac1. Furthermore, the involvement of Rac1 in stretch‐induced glucose uptake has not been investigated.

Methods

We examined the involvement of Rac1 in stretch‐stimulated glucose uptake and signalling in incubated soleus and EDL muscles from tetracycline‐inducible muscle‐specific Rac1 knockout mice.

Results

Passive stretching (15 minutes to 130 mN) increased phosphorylation of Rac1's downstream target, PAKThr423 by ~200% in both soleus and EDL muscles. This response was inhibited by 60% in soleus and 75% in EDL from Rac1 knockout mice. In soleus and EDL, stretch increased 2‐Deoxy‐glucose uptake by 240% and 130%, respectively. This response was decreased in the Rac1 knockout muscles by 30% in soleus and 50% in EDL muscles.

Conclusion

These data show that Rac1 and its downstream target, PAK1 are activated by stretching and are important regulators of stretch‐stimulated glucose uptake in skeletal muscle.
Severe left ventricular dysfunction following short‐term high fat feeding in a canine model
Authors: Nelson Michael , Broussard Josiane , Kolka Cathryn , Bediako Isaac Asare , Szczepaniak Lidia S. , Bergman Richard
Published: June 2021

This study tested the effects of short‐term high fat feeding on left ventricular function. Experiments were conducted in 4 mongrel dogs at baseline (normal chow: 40/30/30 carb/fat/protein), and after 2 and 6 weeks of high fat feeding (30/50/20 carb/fat/protein). Each condition included an intravenous glucose tolerance test for metabolic assessment, along with cardiac magnetic resonance imaging (cMRI) to evaluate left ventricular (LV) volumes, mass, and myocardial deformation (by tissue tagging). Remarkably, 2‐wk of high fat feeding dramatically worsened (all p<0.05) LV ejection fraction (mean+SD;−11.8+6.6%), circumferential strain (CS,+4.6+1.7%), circumferential strain rate (CSR,+34.7+16.0%/s) and LV torsion (−4.3+2.0°), with no changes in LV mass, heart rate, or glucose tolerance. By week 6, LV end‐diastolic volume significantly increased above baseline (+9.3+7.7 mL), returning ejection fraction closer to its basal level (−3.2+1.9%), while CS, CSR, and torsion remained impaired. Mechanisms responsible for impaired cardiac function from a short period of fat feeding with a modest increase in body weight need to be further elucidated.

Support: Heart and Stroke Foundation of Canada (MN), Branco Weiss Fellowship (JB), NIH DK27619, DK 29867.
Effects of Sertoli cells Implantation on Type 2 Diabetes in Nonhuman Primates
Authors: Hansen Barbara C , Cameron Don , Calafiore Riccardo , Luca Giovanni , Linden Ellen H , Szekeres Charles
Published: June 2021

Transplanted allo‐ and xenogeneic Sertoli cells, encapsulated in alginate, have been shown to successfully treat endocrine and neurodegenerative dysfunctions in experimental models with efficacy in the diabetic rodents. In order to determine the translational potential for therapeutic efficacy in humans, we have investigated its application in the spontaneously obese nonhuman primate with naturally‐occurring type 2 diabetes. Isolated Sertoli cells 0.05 to 0.1 × 109 cells/kg from outbred prepubertal piglets were encapsulated in alginate and injected (ip) into insulin‐treated diabetic monkeys. One month following transplantation there was a reduction in fasting plasma glucose, HbA1c decreased by 0.5–1.4% accompanied by a reduction of mean AM nonfasting glucose levels without change in daily insulin therapeutic doses (by design). Results suggest that this novel encapsulated cell transplantation treatment protocol utilizing xenogeneic Sertoli cells may have resulted in a potential positive therapeutic effect on the metabolic status of the diabetic condition which occurred without an apparent inflammatory response. Due to the therapeutic evidence and safety of Sertoli cell transplantation to provide clinical relief in models of diabetes, including the monkey, these data support additional studies in nonhuman primates to further establish potential for successful treatment of diabetes in human.
Methanol extract of Ulmus pumila. L exerts potent anti‐inflammatory effects in murine macrophages and mouse skin
Authors: Ghosh Chiranjit , Yang Seung Hak , Hwang Seong Gu
Published: June 2021

Ulmus pumila.L has been reported to be used as an oriental medicine for treating inflammation for centuries, but the effects and mechanism of its action have not been fully characterized. In this study, we investigated the in vitro and in vivo anti‐inflammatory effect of methanol extract of Ulmus pumila (UP). UP was found to inhibit significantly LPS‐induced nitric oxide (NO) in RAW 264.7 cells. UP significantly reduced the mRNA expression of pro‐inflammatory cytokines including TNF‐α, iNOS, IL‐1β, COX‐2 and IL‐6 in LPS‐stimulated RAW 264.7 cells. Moreover, nuclear translocation of p65 subunit was also dose dependently suppressed by UP treatment. In addition, UP also inhibited phorbol ester‐induced increase in ear swelling and skin water content in BALB/c mice. These results suggest that UP can be a potential candidate for inhibiting inflammation and can be used for the development of new anti‐inflammatory agents.
Calcium Kinetics during Bed Rest with Artificial Gravity and Exercise Countermeasures
Authors: Smith Scott M. , Sceppa Carmen Casteneda , O'Brien Kimberly O. , Abrams Steven A. , Gillman Patti , Zwart Sara R. , Wastney Meryl E.
Published: June 2021

To assess the potential for artificial gravity (AG) and exercise (EX) to mitigate the effects of bone loss during space flight, we performed two studies: (1) a 21‐d bed rest (BR) with subjects receiving 1 h/d AG (n=8) or no AG (n=7) and (2) a 28‐d BR with 1 h/d resistance EX (n=10) or no EX (n=3). In both studies, stable isotopes of Ca were administered orally and intravenously, at baseline and after 10 d of BR, and blood, urine, and feces were sampled for up to 14 d. Tracers were measured using thermal ionization mass spectrometry. Data were analyzed by compartmental modeling. Ca balance during BR (−316±185 mg/d) and BR+AG (−292±141 mg/d) was lower than before BR because less Ca was absorbed. However, Ca balance did not change with BR+EX, even though absorbed Ca decreased and urinary Ca excretion increased, because endogenous excretion decreased and bone deposition increased. Both studies were designed to restrict energy intake during BR (to maintain body weight in the AG study, and to mimic decreased intake in some astronauts in the exercise study). Ca intake was also decreased during BR (by 215 mg/d in the AG study and 112 mg/d in the EX study), resulting in lower absorbed Ca. We conclude that during BR (or space flight) Ca intake needs to be maintained or even increased with countermeasures such as exercise, to enable maintenance of bone Ca. These studies were funded by NASA and NSBRI.
Essential Genes in the Development and Maintenance of the Temporomandibular Joint
Authors: Purcell Patricia , Hill Adele , Jheon Andrew , Vivero Matthew , Duran Juanita , Tabin Clifford J , Klein Ophir D , Warman Matthew L
Published: June 2021

The temporomandibular joint (TMJ) is a highly specialized synovial joint essential for the mobility and function of the mammalian jaw. The TMJ is a complex unit, composed of the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between the two bones. A fibrous capsule links these two bones and maintains the cavity filled with synovial fluid. The genetic program for the development and maintenance of the TMJ is yet to be elucidated. Using laser capture micro‐dissection, followed by genome‐wide expression analysis, we have identified two signaling pathways that are crucial in TMJ formation. Gli2, from the Hedgehog signaling pathway, is essential in TMJ disc morphogenesis, whereas, Spry1 and Spry2, inhibitors of receptor tyrosine kinase signaling, are critical in cranial muscle and fossa development. The TMJ synovial fluid provides lubrication to the joint. Lubricin, a product of the gene proteoglycan 4 (Prg4), is the major component of the synovial fluid. We have found that in embryos and newborn mice lacking lubricin, their TMJs appear normal, while in adult mice we observe a premature osteoarthritis‐like disease of the joint that becomes more severe as the mice age. Thus, our findings demonstrate the importance of two signaling pathways in TMJ morphogenesis and identify the Prg4 gene as essential for maintenance of a functional and healthy TMJ.
Early intestinal colonization phenotypes predict necrotizing enterocolitis in preterm infants
Authors: Morrow Ardythe L , Lagomarcino Anne J , Schibler Kurt R , Taft Diana H , Yu Zhuoteng , Wang Bo , Gevers Dirk , Ward Doyle V , Kennedy Michael A , Huttenhower Curtis , Newburg David S
Published: June 2021

Necrotizing enterocolitis (NEC) afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to subsequent NEC onset is not understood. We analyzed prospectively banked samples collected prior to disease onset from infants <29 wks gestational age, including 11 who developed NEC and 21 matched controls who survived free of NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing. Two forms of dysbiosis preceded NEC. During postnatal days 4 to 9, the samples from 4 NEC cases were dominated by phylum Firmicutes (relative abundance: >;99% vs <15% in the remaining NEC and controls, p<0.001). During days 10 to 16, samples from the remaining NEC cases were dominated by phylum Proteobacteria (relative abundance >;99% vs 39% in the other NEC cases and 84% in controls, p=0.01). NEC preceded by Firmicutes dysbiosis occurred during postnatal days 7 to 21, whereas NEC preceded by Proteobacteria dysbiosis occurred later, days 19 to 39. Metabolomic analysis of urine samples from days 4 to 9 identified metabolites that predicted onset of one the two microbially‐defined NEC types vs controls (p<0.01), but no metabolites differed between all NEC cases and controls. Distinct forms of dysbiosis may help predict NEC well in advance of onset, providing clues to the underlying pathobiology.

Project funded by NIH HD 05491, NIH T32 ES 010957–12, and NIAID NIH HHS Contract No. HHSN272200900018C
Effect of Nuts on Coronary Heart Disease Risk Factors in Type 2 Diabetes
Authors: Kendall Cyril WC , Augustin Livia SA , Bashyam Bala , Nishi Stephanie , Jenkins David JA
Published: June 2021

Background

Nut consumption has been associated with a reduced risk of coronary heart disease (CHD). In a recently completed clinical study we found that nut consumption significantly improved glycemic control and blood lipid risk factors for CHD compared to a healthy control.

Objectives

To determine if tree nuts improve other markers of cardiovascular risk including serum fatty acid profile, LDL particle sixe, clotting factors and markers of oxidative stress.

Methods

117 subjects with type 2 diabetes were randomized to a 3‐month parallel design study. Subjects were randomized to one of three treatments: 1) Test (Full Dose Nut Diet): 75g/d for 2,000kcal/d; 2) Test (Half Dose Nut Diet): half‐dose of nuts and half‐dose of control muffin; and 3) Control: whole wheat muffins matched with energy content of nut supplements. Fasting blood samples were collected at baseline and weeks 2, 4, 8, 10 and 12 for markers of glycemic control and CHD risk factors.

Results

Compared to the control, the full dose nut supplement significantly lowered HbA1c (P=0.039), total‐C (P=0.002), LDL‐C (P=0.007), total‐C:HDL‐C (P=0.015), and LDL‐C:HDL‐C (P=0.028). Data on other markers of cardiovascular risk will be presented.
Leptin as a marker of undernutrition in breast cancer recurrence
Authors: Bard Jean‐Marie , Lefrançois Armelle , Jaffre Isabelle , Joalland Marie‐Pierre , Classe Jean‐Marc , Campone Mario , Bobin‐Dubigeon Christine
Published: June 2021

Objective

To relate leptin concentration with undernutrition and survival time in breast cancer recurrence.

Design and methods

Leptin and other markers of undernutrition were measured in 49 patients who experienced disease recurrence for breast cancer. Undernutrition was clinically assessed by a weight loss of ≥10% between primary diagnosis and recurrence or ≥5% within the last month and/or the prescription of food supplements. Results were compared between patients with (21) or without (28) undernutrition by logistic regression models. The effect of biological variables on survival rate was assessed by the Kaplan‐Meier method.

Results

Leptin was significantly and negatively associated with undernutrition (OR=0.45 [0.23–0.87], p=0.018), while PINI (Prognostic Inflammatory and Nutritional Index, OR=1.24 [0.94–1.63], p=0.130) did not reach significance. The survival distributions across quartiles of leptin (Log rang test, p=0.048) and PINI (Log rank test, p=0.0001) were significantly different. However, as assessed by the Cox proportional hazards models, quartiles of leptin did not differ between each other while quartiles of PINI were all significantly different from quartile 1.

Conclusion

In case of breast cancer recurrence, leptin is a good marker of undernutrition but is a poor marker of survival time, while PINI is a poor marker of undernutrition but is a good marker of survival time.
Model‐based Compartmental Analysis of Vitamin A Kinetics in Vitamin A‐Supplemented Neonatal Rats Predicts Extensive Recycling and Altered Inter‐compartmental Exchange Rates
Authors: Tan Libo , Green Michael H , Ross A. Catharine
Published: June 2021

Compartmental modeling has contributed greatly to our understanding of vitamin A (VA) metabolism in adult animals and humans. However, VA metabolism in neonates is virtually uncharacterized. Our objective was to develop a whole‐body model of VA metabolism in placebo and VA‐supplemented neonatal rats, taking into account their inherent metabolic non‐steady state. We hypothesized that VA supplementation perturbs retinol kinetics and alters tissue VA distribution in neonates. On postnatal day 4, pups (n=3/time point) received 11,12‐[3H]retinol orally, admixed with either oil (placebo) or VARA (VA+10% retinoic acid [RA]). Plasma and tissues were collected at selected time points. A multi‐compartmental model as viewed from the “plasma space” indicated extensive recycling of retinol between plasma and tissues in neonates, as in adults. The recycling was, however, much faster in neonates. VARA decreased the turnover of retinol between plasma and extravascular tissues. Compartmental models for various organs were also developed. The models indicated that, in neonates, tissues other than liver are important in taking up retinyl ester from chylomicrons, and this is further stimulated by VARA supplementation. NIH HD‐66982

Grant Funding Source: NIH
Educational internships: Extra‐curricular opportunities to enhance graduate employability
Authors: Lewis David Ian
Published: June 2021

The “Working towards your Future” report recommended that Universities provide opportunities, both within and outside of the curriculum, for students to develop employability skills and gain work experience. We therefore developed a programme of educational research internships, outside of the taught curriculum, which enable students develop a different set of employability skills to those gained within the laboratory.

Students undertaking these internships contribute to ongoing programmes of educational research e.g. evaluation of young people's opinions of the use of research animals; use of tablet devices in practicals; development of a wiki of ethics OERs.

Students are required to regularly reflect during their internship and write a short case study on completion. In these, they recognise the skills gained and the benefit of these to their future employability; they also have a tangible outcome or resource they can show to prospective employers. Educational research internships are therefore a valuable means outside of the taught curriculum for students to develop employability skills and to gain work experience. They also provide significant benefits for the Faculty in enhancing the student learning experience, facilitating pedagogical and educational research and in the external promotion of its activities.

The financial support of the Leeds for Life Foundation is gratefully acknowledged.
“Sex‐specific microRNA networks in cardiac hypertrophy”
Authors: Burton Tyler , Malone Payton , Baute Audrey , Waikel Rebekah
Published: June 2021

Sex differences in cardiovascular disease, susceptibly and progressively, including left ventricular hypertrophy (LVH) and subsequent heart failure, have been well documented. MicroRNAs (miRNAs), which have been shown to be regulated during LVH, might provide insight into these sex differences. To establish sex‐specific miRNA profiles in LVH, male and female C57BL6 mice were subjected to transaortic constriction (TAC). Two‐weeks postsurgery, mice were euthanized and heart weights were determined. Male mice had significantly greater levels of cardiac hypertrophy as compared to female mice. Total RNA was isolated from left ventricular tissue samples, and next generation sequencing was performed on small RNAs. Comparing miRNA expression data from TAC, sham surgical, and non‐surgical animals, we have established unique sex‐specific miRNA expression profiles in left ventricular hypertrophy and in a non‐surgical state. We have used these profiles to establish potential signaling networks responsible for sex‐differences. Functional significance of networks known to influence cardiac hypertrophy, including TGFβ and MCIP1, are currently being investigated. It is anticipated that establishment of sex‐specific miRNA networks will aid in the use of miRNAs as diagnostic and therapeutic targets for LVH.

NIH 5P20RR016481–12, 8P20GM103436–12, R15HL108192–02
VIRAL SATELLITE RNA AS A BIOLOGICAL CONTROL AGENT FOR PLANTS
Authors: Montasser Magdy S.
Published: June 2021

Biological control technology based on viral satellite mediated protection is a novel concept of the viral disease control strategies. Cucumber mosaic virus (CMV) is considered one of the most economically damaging viruses among field grown vegetables such as tomato (Solanum lycopersicum L). CMV can harbor molecular parasites known as satellite RNAs that dramatically alter the symptom phenotype induced by the virus. Two indigenous strains of CMV satellite RNA were isolated and have been sequenced. One of these strains designated as CMV‐KU1 reduced the viral disease to a virtually asymptomatic condition. The other strain was found to aggravate the symptoms and cause severe crop loss and tomato necrosis. Thus, satellites have been referred to as “natural inhibitors of crop damaging viruses’. These satellites RNAs are small nucleic acids whose nucleotide sequences are unrelated to, but are replicatively dependent upon the viral genome; they have a molecular parasitic relationship. Particularly, the KU1 strain may be used to protect plants against a particular viral strain of CMV, referred to as the KU2 strain. The attenuating properties of some satellite RNAs can be exploited to control viral diseases by preinoculating crops with an attenuating satellite RNA variant combined with virus. This technique can effectively protect against CMV disease in the field.
ABCD3 Gene Important In Prostate Cancer
Authors: Reams Romonia Renee , Jones_Triche Jacqueline , Wang Honghe , Soliman Karam F.A. , Yates Clayton Clopton
Published: June 2021

African American men have higher rates of prostate cancer morbidity and mortality than men of other racial or ethnic groups in the US and globally. We favor genetics as the factor that explains prostate cancer health disparity in Black men. The objective of our study was to interrogate cDNA microarray data comparing gene expression profiles in AA and EA to hunt for gene or gene signatures that are associated with aggressive Prostate cancer. Bioinformatic interrogation of our genomic microarray data identified ABCD3 expression as significantly associated with African American prostate tumors. Our findings implicated involvement of three network hubs, centered on ERK, Mapk and NFkB signaling pathways. We further demonstrated that ABCD3 expression increased with increasing metastatic potential in a panel of novel CaP cells lines. We observed increased ABCD3 expression in more aggressive tumors compared to normal prostate tissue in a large patient cohort. Lastly si‐ABCD3 treatment in MDA‐PC‐2b cells resulted in a significant decrease in proliferation as well as enhanced chemosensitivity to Paclitaxel. Thus, ABCD3 appears to play an important role in aggressive CaP progression.
Intake of CLA‐fortified butter decreases serum levels proinflammatory mediators in healthy subjects
Authors: Penedo Leticia Abel , Torres Alexandre Guedes , Quírico‐Santos Thereza , Nunes Juliana
Published: June 2021

Conjugated linoleic acid (CLA) isomers are bioactive lipids, which affect risk factors associated with chronic sub‐clinical inflammation. We aimed to investigate the effect of supplementation of 1g/ day of c9,t11 CLA, through the daily intake of a fortified butter, on the serum levels of insulin, interleukin (IL)‐ 2, IL‐8, TNF‐α and on the activity of metalloproteinases of matrix extracellular (MMP)‐2 and MMP‐9, of 29 (13 men) healthy young (29 ± 6 yrs) adults. The experimental design consisted of a depletion‐repletion study, in which the voluntaries were 8 weeks without dairy intake and consecutive 8 weeks with habitual consumption of dairy products associated with CLA‐fortified butter intake. The consumption of the CLA‐fortified butter significantly reduced serum levels of IL‐2 (−31±2,1%), IL‐8 (− 26±3,2%) and TNF‐α (−22±1,8%). In addition, the activity of both MMP‐2 (−32±2,7%) and MMP‐9 (−32±1,9%) were also reduced (P<0.05). Taken together, our results indicate that the intake of c9,t11 CLA enriched butter by normal‐weight humans were able to promote immunomodulation via decreasing inflammatory mediators, that are usually associated with the chronic sub‐clinical inflammation observed in overweight individuals.
Dietary Micronutrient Intake of Pulmonary TB patients in Tbilisi, Georgia
Authors: Frediani Jennifer K , Tukvadze Nestani , Sanikidze Eka , Gegechkori Maia , Kempker Russell R , Millson Erin C , Hebbar Gautam , Blumberg Henry M , Ziegler Thomas R
Published: June 2021

Aim

To obtain information on habitual dietary intake of selected micronutrients in TB patients in Tbilisi, Georgia.

Method

Dietary intake was obtained from patients at TB diagnosis using a tool that captures specific foods common in Georgian culture. Foods consumed during the previous 3 days were determined by one‐on‐one interviews. Food intake data was entered into the NDS‐R software program and mean daily micronutrient intake determined. Descriptive statistics and intake of micronutrients compared to the United States Dietary Reference Intake (US DRI) guidelines for adults and food group frequency were evaluated.

Results

A total of 199 subjects were studied (mean age 34 y; 64% male). No subject consumed specific micronutrient supplements. Mean daily intake of vitamin D 186±173(SD) IU/day (31% of US RDA); retinol (vitamin A) 686±600 mcg/day (84% of US RDA), vitamin E 19±9 IU/day (85% of US RDA); manganese 4.56±1.74 mg/day (217% of US AI); copper 2.28±1.01 mg/day (253% of US RDA), selenium 147±65 mcg/day (267% of US RDA) and zinc 12.2±5.3 mg/day (125% of US RDA). Dietary intake of both thiamine (vitamin B1) and riboflavin (vitamin B2) was adequate at 2.4±0.9 mg/day (209% of US RDA) and 2.6±1.0 (216% of US RDA), respectively.

Conclusions

Dietary intake data from these Georgian TB patients revealed adequate intake of the B vitamins thiamine and riboflavin, and specific trace elements linked to human immune function (copper, selenium, and zinc). In contrast, dietary intake of several vitamins linked to immune function (vitamin D, retinol and vitamin E) was inadequate.

Grant Funding Source: NIH D43 TW007124, D43 TW007124‐06S, K24 RR023356, UL1 RR025008, Emory Global Health Institute
Potassium Intake of the U.S. Population, What We Eat In America, NHANES 2009–2010
Authors: Hoy M. Katherine , Goldman Joseph D.
Published: June 2021

Potassium is identified in the 2010 Dietary Guidelines for Americans as a nutrient to be increased in the diet, and the Institute of Medicine's Adequate Intake (AI) recommendation is set at 4,700 mg per day for adults. To describe the potassium intake of the U.S. population, data were analyzed from 1‐day food intakes of individuals 2+ years, excluding breastfed infants (N=9042) in What We Eat In America, NHANES, 2009–2010, and the contribution of different foods to population total potassium intake was determined. On the reporting day, the mean (SE) intake was 2640 (18) mg; adult males 20+ years (N=2789) consumed 3172 (44) mg and adult females 20+ years (N=2973) consumed 2408 (22) mg. Potassium density (mg/1000 kcal) was higher in the diets of females compared to males (p<0.0001). Compared to whites and Hispanics, blacks consumed less potassium (−338 mg, p<0.0001); there was no difference between intakes of whites and Hispanics. The top foods contributing to potassium intake were fruits and vegetables (20%), milk and milk drinks (11%), meats and poultry (10%), grain‐based mixed dishes (10%), coffee and tea (7%). By age, the highest contributors to potassium intake were milk and milk drinks for children 2–5 years (27%) and 6–11 years (22%), mixed dishes for adolescents 12–19 years (20%), and fruits and vegetables for adults 20+ years (21%). These data can inform monitoring of population dietary intake and dietary guidance.
The changes of chemerin and chemerin receptor to regulate lipid metabolism in liver and pituitary gland
Authors: Roh Sanggun , Kitayama Shun , Ardiyanti Astrid , Suzuki Yutaka , Yamauchi Eri , Kato Daiki , Yi Kwonjung , So Kyoungha , Hagino Akihiko , Katoh Kazuo
Published: June 2021

Chemerin was identified as a novel adipokine highly expressed in adipose tissue, suggesting that it plays a role in the pathophysiology of obesity. Chemerin actions are primarily mediated through binding to receptor expressed in several tissues. Likewise, chemerin expression has been detected in a variety of extra adipose tissues, including liver and pituitary. However, the expression and regulation of chemerin and its receptor mRNA in the liver and pituitary as a link in the lipid metabolism were not cleared. Chemerin function at the liver and pituitary was assessed by analyzing the expressions of both chemerin and chemerin receptor gene. The levels of chemerin and chemerin receptor mRNA was not changed in the liver in mice fed high fat diet compared with normal diet. However, these genes were upregulated in the adipose tissue in mice fed high fat diet. Chemerin mRNA expression was down‐regulated in pituitary gland in mice fed high fat diet, however chemerin receptor was not changed. Chemerin gene expression was up‐regulated in pituitary during 12 h of fasting, while chemerin receptor was not affected. Insulin and glucose treatment for 6h in HepG2 cells increased chemerin gene expression. These results suggest that that chemerin, either locally produced from the liver and pituitary, may play an endocrine role in the control of lipid metabolism via its own receptor.
K/BxN‐induced poly‐arthritis is exacerbated by infection with the intestinal helminth parasite Hymenolepis diminuta; possible involvement of complement and mast cells
Authors: Graepel Rabea , Jirik Frank R , Sharkey Keith A , McDougall Jason J , McKay Derek M
Published: June 2021

We examined the effect of Hymenolepis diminuta (H.D.) infection on a model of polyarthritis, to determine if helminth therapy modulates joint inflammation. BALB/c mice were untreated or infected with 10 H.D. cysticercoids. After 8 days, polyarthritis was induced and joint swelling was measured for 13 days. At necropsy, joints and serum were collected for analysis. K/BxN treatment induced swelling of all joints compared to vehicle treatment. Front paws and knees of H.D. infected mice were significantly more swollen than those of non‐infected K/BxN‐treated mice. This was accompanied by significant increases in serum complement C5a and mast cell protease‐1 in H.D. + K/BxN‐treated mice on day 2 compared to control and K/BxN‐only treated mice. Thus, exacerbated inflammation is paralleled by evidence of increased mast cell activation in H.D. + K/BxN treated mice. Mast cell activation is crucial in the K/BxN model and increased activation may underlie the exacerbation of disease by H.D.. Our data indicate that autoimmune pathways may be differentially sensitive to helminth therapy. Research was conducted with the support of Foreign Affairs and International Trade Canada and a CIHR operating grant.
Modulation Of The Baroreflex Depressant Effect Of Chronic Nicotine In Female Rats By Nitric Oxide Synthase And Heme Oxygenase
Authors: El‐Mas Mahmoud M , El‐Gowelli Hanan M , Fouda Mohamed A , El‐Gowilly Sahar M
Published: June 2021

Nicotine impairs reflex chronotropic activity in female rats. Here, we sought evidence to implicate nitric oxide synthase (NOS) and/or heme oxygenase (HO) in the nicotine effect. Baroreflex curves relating chronotropic responses to reciprocal changes in blood pressure were generated by the vasoactive method (phenylephrine and nitroprusside) in nicotine‐treated female rats in absence and presence of NOS/HO pharmacological modulators. Slopes of the curves served as a measure of baroreflex sensitivity (BRS). Nicotine (2 mg/kg/day for 14 days) reduced BRS compared with saline‐treated rats. Findings that favor the involvement of NOS inhibition in the nicotine attenuation of BRS were (i) NOS inhibition (L‐NAME) reduced BRS in saline‐ but not in nicotine‐treated rats, and (ii) L‐arginine, NO donor, reversed the BRS inhibitory effect of nicotine. HO inhibition (protoporphyrin IX, ZnPP) had no effect on BRS in nicotine‐ or saline‐treated rats; it also failed to reverse the beneficial effect of L‐arginine on nicotine‐BRS interaction. Hemin (HO inducer) but not CORM‐2 (carbon monoxide releasing molecule) abolished the BRS attenuating effect of nicotine. Thus, the inhibition of NOS, but not HO, is causally related to nicotine‐evoked BRS depression. The latter can also be alleviated after HO induction.

This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No. 502.
Baroreceptor unloading converts depressor responses elicited from the hypothalamic arcuate nucleus to pressor responses
Authors: Kawabe Tetsuya , Kawabe Kazumi , Sapru Hreday N
Published: June 2021

The type of response elicited from the hypothalamic arcuate nucleus (ARCN) depends on the level of baroreceptor activity. It was hypothesized that baroreceptor unloading may determine the type of response elicited from the ARCN. This hypothesis was tested in urethane‐anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN to increases in MAP and GSNA and exaggerated tachycardia. Microinjections of ionotropic glutamate receptor antagonists into the paraventricular nucleus (PVN) in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated tachycardia. Microinjections of a melanocortin 3/4 receptor antagonist into the PVN in barodenervated rats attenuated increases in MAP, GSNA and heart rate elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alphamelanocyte stimulating hormone (alpha‐MSH) and adrenocorticotropic hormone (ACTH).

Conclusion

increases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha‐MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN. Support: NIH grants HL024347 and HL076248(HNS).
Finding a Correlation Between the Deltoid Tuberosity & Torsion Angle in the Humerus
Authors: De Leon Monica Maria , Kimble Mabel Michelle , Giljum Karl , Nusse Gloria
Published: June 2021

How does muscle orientation and torsion angle affect movement in the shoulder and brachium, as illustrated by the location of the deltoid tuberosity? Using the San Francisco State University teaching collection, we examined 15 left humeri, and focused on their total morphology. The purpose of this study is to find a significant correlation between the torsion angle of the humerus, and deltoid tuberosity. Torsion angle describes the innate twisting found in the humeri, and plays a significant role in our posture. Using Evans and Krahl's (1945) methodology, we calculated the torsion angles by creating a “torsio‐ meter”; using a platform to stabilize the humeri, and two laser beams to cross the tangent lines. Dissected human cadavers and intact skeletons were also examined to further investigate this relationship. The results showed significant amount of variability between all of the humeri in their morphology. These differences were analyzed in order to understand how torsion angle might affect muscle insertion of the deltoid. While the lengths, widths, torsion angles, and landmark orientations are unique in each humeri, and certainly play a role in physical performance, we are investigating this one aspect of correlation between the deltoid tuberosity and torsion angle.

Grant Funding Source: None
Variants of sacral spina bifida occulta
Authors: Singh Rajani
Published: June 2021

Precise and systematic knowledge of normal and classified variant anatomy of sacral spina bifida occulta is clinically important for anesthetists, neurologists, radiologists, orthopedic surgeons and academically to anatomists for correlating classes, their genesis and clinical implications. Therefore the study has been carried out. 85 dry sacra were examined, classified in five categories, genetic causes analysed and associated clinical significance was correlated for sacral spina bifida occulta

Type‐I the dorsal wall is completely open, Type‐II the dorsal wall is open below S1 down to S5. Type‐III the dorsal wall is open from S2 to S5. Type‐IV the dorsal wall is open below S3 down to S5, Type‐V the dorsal wall is open between S1 and S2. The cause for the genesis of this defect was attributed to the combined effect of mutation of Pax1/Pax9 pair, Hox11 and Foxc genes derived from genetic studies on mice besides environmental factors.
Metabolic Disorder in a Mouse Model on an American Diet: Proteomic Analysis of Cardiovascular Disease
Authors: Whelan Stephen A. , McComb Mark E. , Spencer Jean L , Heckendorf Christian F. , Bachschmid Markus M , Siwik Deborah A. , Colucci Wilson , Cohen Richard A. , Costello Catherine E.
Published: June 2021

Unfavorable metabolic conditions (metabolic disorders) associated with obesity, diabetes, and hyperlipidemia are major causes for cardiovascular disease (CVD). One major environmental cause of this may be attributed to poor diet, aka the American diet. The early detection and monitoring of the adverse effects of metabolic disease on the heart and vasculature, although well studied, remain elusive. Our hypothesis is that poor diet causes unfavorable metabolic conditions in heart tissue resulting in inflammation and oxidative stress reflected in protein changes. Here we apply label‐free proteomics to elucidate potential biomarkers of CVD including both protein changes and changes in post‐translational modifications (PTMs). Heart tissue was from control mice and mice fed a high fat high sucrose diet (HFHS). MS/MS data was analyzed with Proteome Discoverer and Mascot software, using both variable‐modification and error‐tolerant search modes. Label‐free quantification was conducted using Scaffold and Progenesis; typically yielding >;1,000 features. Using IPA software revealed a number of cardiovascular disease related proteins were observed. This is the first step in biomarker panel development for disease diagnosis and progression. This project was funded by NIH‐NCRR grants P41 RR010888/GM104603, S10 RR015942, S10 RR020946, S10 RR025082 and NIH‐NHLBI contract N01 HV00239.
Iron deficiency and physical activity after a dietary iron intervention in female Indian tea pickers
Authors: Serrano Yosmel , Rahn Maike , Crump Erica , Venkatramanan Sudha , Haas Jere D.
Published: June 2021

The objective of this study is to examine the effect of a double‐fortified salt (DFS) (containing iron and iodine) intervention on iron status and physical activity in female Indian tea pluckers. A double‐blinded study randomized 217 women working at a tea estate in West Bengal, India to consume either iodized salt fortified with iron (DFS) or iodized salt (control) for 10 months. The DFS group received approximately 5–7 mg iron/day. Iron status (Hb, sFt, sTfR), inflammation markers (CRP, AGP), and physical activity levels (estimated through Actigraph accelerometers) were determined at baseline and end line data collection. Physical activity was categorized by the number of minutes spent in sedentary physical activity (1.00 MET), light physical activity (1.01–2.99 METs), and moderate‐to‐vigorous physical activity (>;3.00 METs) at work and discretionary (before work, after work, and during break) time. There was a significant increase in sFt (p=0.02) and body iron (p=0.004) from baseline to end line in the DFS group compared to control group. The DFS group showed a significant increase in minutes spent in total discretionary time (p=0.0136) in light physical activity. We conclude that consumption of DFS improved iron status and had a positive effect on leisure activities.

Funded by the Mathile Institute for the Advancement of Human Nutrition and the Micronutrient Initiative.
Weight and Percent Body Fat Increased Significantly over Freshman Year in a Subset of the FLASH College Health Study
Authors: Pride Adrienne , Hey David , Hagobian Todd , McDermott Ann Yelmokas , Hall Laura Marie
Published: June 2021

College Freshman are at a critical point in their lives where they are establishing health behaviors that can last a lifetime. On average, adults in America gain 0.4 to 1.8 pounds per year, referred to as “creeping obesity”. Our purpose was to determine students’ perceptions of their resting energy expenditure (REE), record actual REE, body composition, and weight changes longitudinally over two time periods (Fall 2011 and Spring 2012) during their Freshman year at Cal Poly, San Luis Obispo, CA using a subsample of the FLASH College Health Study (N=39 Females). REE was measured using the BodyGem™, body composition was measured using bioelectrical impedance analysis (BIA), and weight and height were measured to calculate BMI. We found a significant increase in weight from 59±7kg to 60±7kg (p=0.0489) and percent body fat from 27±5% to 30±4% (p<0.0001) over their Freshman year. When comparing perceived REE to measured REE, students slightly overestimated calories at both visits (~163 kcals over, p=0.0091 and ~142 kcals over, p=0.0335, respectively), however, demonstrating that they were quite good at estimating their REE. Overall Freshman students gained approximately 1 kg which could potentially have adverse health consequences.

Funding: Agricultural Research Institute (ARI) Grant (47861)
Estimated vs. actual resting energy expenditure and physical activity factor in post‐gastric bypass, lean and obese adults
Authors: Ramirez‐Marrero Farah A , Edens Kim , Curry Timothy B , Joyner Michael J
Published: June 2021

Resting energy expenditure (REE) equations multiplied by a predetermined physical activity factor (PAF) are commonly used to determine energy requirements However, estimated vs. actual REE and PAF among post‐gastric‐bypass surgery (GBS), obese (Ob) and lean (L) adults have not been compared. We hypothesized that GBS, Ob and L adults will have: 1) actual REE lower than estimated and 2) actual PAF lower than estimated. A group of 13 GB, 15 Ob and 11 L adults completed REE measurements by indirect calorimetry following standard clinical procedures. The Harris‐Benedict equation (HB) and pre‐determined PAF were used to estimate energy requirements. Physical activity energy expenditure (PAEE) was determined with accelerometry and PAF with the equation: (Actual REE + accelerometry PAEE)/Actual REE. Two‐way ANOVAs were used to detect differences by group and method, and agreement between methods using Bland & Altman plots. Group differences in actual REE (1631±174, 1830±290, 1441±151 kcal/day, respectively; P<0.01) and HB REE (1600±131, 1970±274, 1542±225 kcal/day, respectively, P<0.01) were observed, with no differences by method. Actual PAEE (269±70, 365±98, 228±112 kcal/day, respectively, P=0.002) yielded PAF ranging from 1.1 to 1.3, while HB PAF ranged from 1.2 to 1.7; causing higher predicted vs. actual energy requirement in all groups. While HB REE appeared adequate, predetermined PAF are not recommended.
Anti‐inflammatory Activities of Plant pigments
Authors: Kim Jong‐Sang , Kang Hye Ryung , Kim Hyo Jung , Seo Ji Yeon , Park In Sil , Kim Seong Soon , Kim Bo Ram , Zakharova Alexandra
Published: June 2021

Natural colorants have become substantially popular as consumers are getting more interested in safety and wellbeing. As plant pigments have not been widely studied for their bioactive function, we attempted to evaluate the anti‐inflammatory activities of 24 kinds of plant‐derived colorants which were prepared by extraction with hot water. Among 24 kinds of samples, lac Dye, pagoda flower, deyer weed, dragons blood, and logwood showed relatively strong anti‐inflammatory effect. They effectively inhibited production of nitric oxide (NO) and inflammatory cytokines, and suppressed expression of inducible nitric oxide synthase (iNOS), cyclo‐oxygenase‐2 (COX‐2), and phosphorylation of nuclear factor (NF)‐kappa B p65 in lipopolysaccharide (LPS)‐treated murine macrophage Raw264.7 cells. In addition, we confirmed the suppression of TPA‐induced skin inflammation by the samples in a mouse model. These findings suggest that the five samples exert anti‐inflammatory action through the inhibition of NF‐kappa B signaling pathway.

Grant Funding Source: Ministry of Knowledge Economy
Hypo‐Osmolality Pressor Stimulus is Linked to Transient Receptor Potential Vanilloid 4 (TRPV4) in the Portal Region
Authors: Mai Tu , McHugh Julia , Diedrich Andre’ , Garland Emily M , Robertson David
Published: June 2021

Patients with baroreflex impairment have a robust and sustained increase in blood pressure (BP) after water consumption. Using a sino‐aortic denervated mouse model (SAD), we identified hypo‐osmolality as the stimulus for this osmopressor response (OPR). However, the mechanism of the OPR is still unclear. We tested the hypothesis that decreased osmolality is sensed in the portal area after water consumption and that TRPV4 channels are essential for the response. We infused 0.45% or 0.9% saline directly into the portal vein of SAD wild type (WT) and TRPV4−/− mice. An immediate pressor response occurred in WT mice after 0.45% saline but not after 0.9% saline infusion (0.45%: 16 ± 6 vs. 0.9%: − 6 ± 2 mmHg, p=0.03). On the other hand, infusion of 0.45% saline into TRPV4−/− mice failed to stimulate a pressor response (−5 ±2 mmHg, p=0.03 for comparison with WT). We further explored the possible mechanism of OPR by using celiac ganglionectomized (CGX) and sham WT mice. Both CGX and sham mice had a robust increase in BP after water infusion into the duodenum (CGX: 10 ± 2 vs. SHAM: 12 ± 1 mmHg, p=0.5). However, the response was shortened by ganglionectomy. Ten minutes after water, BP had returned to normal in CGX, while it remaining elevated in sham mice (CGX: 0.3 ± 2 vs. 9 ± 1.7 mmHg, p=0.01). We conclude that TRPV4 channels in the portal region are essential for the OPR, and the celiac ganglia play an important role in maintaining BP elevation.
Inhibition of Neutral Sphingomyelinase Prevents High Pressure‐Induced Shift in the Mediator of Endothelium‐Dependent Dilation from NO to H2O2
Authors: Freed Julie K. , Beyer Andreas M. , Gutterman David D.
Published: June 2021

We have shown that ceramide, a product of neutral sphingomyelinase, (N‐SMase) causes a transition from nitric oxide (NO) to hydrogen peroxide (H2O2) as the mediator of flow‐mediated dilation (FMD) in arterioles from healthy subjects. We tested the hypothesis that the stress of an elevation in intraluminal pressure similarly alters the mediator of FMD. Human arterioles (100–200μm diameter) were prepared for videomicroscopy. L‐NAME inhibited FMD (max dilation=24.6±7.6 vs. 82.6±4.9, n=6, p<0.01, *t‐test), whereas FMD was unaffected by L‐NAME following exposure to 150mmHg of intraluminal pressure (HP) for 30 min (71.8±5.9, n=7). Under control conditions, PEG‐Catalase (500 U) did not affect FMD (74.8±8.6, n=6), but after HP, FMD was reduced (23.8±6.1, n=6, p<0.01*). Treatment with the specific N‐SMase inhibitor GW4869 (4μM; 12 hours) did not alter FMD (79.9±11.3, n=3) vs. control (82.6±4.9, n=6), however FMD was attenuated post‐HP in the presence of GW4869 (33.9±6.7, n=3). Post‐HP, in GW4869‐treated vessels, FMD was blocked by L‐NAME (12.5±6.2, n=3) but tended to improve with catalase (48.6±9.4, n=3). These data suggest that N‐SMase is capable of altering the mechanism of FMD from NO to H2O2 following acute elevation of pressure.