bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced insulin sensitivity limits reductions in small dense LDL due to lean beef consumption (821.14)
Authors: Wu Xiuzhi , Roussell Michael , Smith Stephen , Kris‐Etherton Penny , Walzem Rosemary 
Published: June 2021

Atherogenicity of small dense LDL (e.g. LDL‐4) is attributed to their ready penetration of the artery wall &amp; reduced oxidative stability. We tested the effect of beef consumption on lipoprotein (Lp) density distribution in two beef feeding trials. Trial1, 27 subjects consumed in random order: Healthy American diet (HAD), Dietary Approaches to Stop Hypertension (DASH), Beef in an Optimal Lean Diet (BOLD) and BOLD plus extra protein (BOLD+) (20, 28, 113, 153g lean beef/d, respectively, all diets ~30 EN% fat) for 5wks. Trial 2, 25 men consumed in random order: 5‐114g, 24% fat beef patty/wk for 5wks of both low and high MUFA beef patties(Patty, 62 g lean beef/d, 40 EN% fat diet). Density profiles of NBD‐ceramide labeled Lp were imaged following isopycnic ultracentrifugation. Compared with HAD, DASH and BOLD diets decreased HDL‐2b (p<0.05), while BOLD+ only reduced LDL‐4 (p<0.05). Trial 2 found no general diet effect on Lp subclass compared to baseline. Stepwise multiple linear regression of data from both trials identified diet treatment (p<0.0001) and baseline HOMA‐IR [(fasting glu/fasting insulin)/22.5] (p<0.0001) as predictors of LDL‐4 change from baseline. Lower baseline HOMA‐IR &amp; consumption of DASH, BOLD or BOLD+ diets corresponded to a greater reduction in LDL‐4 (p<0.0001). In summary, a heart healthy diet rich in lean beef decreases CVD risk (in part by decreasing LDL‐4) in insulin sensitive individuals.Grant Funding Source: National Cattleman's Beef Association
Effects of fat sources on high fat induced changes in inflammation and lipid metabolism in juvenile pigs (822.3)
Authors: Jang Saebyeol , Molokin Aleksey , Urban Jeseph , Solano‐Aguilar Gloria 
Published: June 2021

Effects of fat sources on high fat induced changes in inflammation and lipid metabolism in juvenile pigs Saebyeol Jang1, Aleksey Molokin1, Joseph F. Urban, Jr. 1, Gloria Solano‐Aguilar1: 1USDA, ARS, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD 20705 The goal of this study was to examine effect of anhydrous milk fat (AMF) and palm oil (PO) on the high fat induced changes in inflammation and lipid metabolism in juvenile pigs. Four‐week‐old conventional crossbred pigs were fed with either a low 10.8% fat (LF) or high 39.5% fat (HF) diets including AMF or PO as their main fat source for 18 weeks . Data was analyzed using Two‐Way ANOVA to determine main effect of fat source (AMF vs PO) or fat level (low vs high fat). Serum lipid panel analysis showed that cholesterol, HDL, and LDL levels were increased in high fat groups. In liver, expression of inflammatory genes including TNFα, iNOS and TLR4, was increased by high fat diets and mRNA expression of MCP‐1 was decreased in LF‐AMF and HF‐AMF (main effect of fat source, p = 0.01). High fat diets also decreased expression of lipogenic genes SCD1 and FASN in liver whereas increased SCD expression in isolated peripheral adipocyte. The mRNA expression for IL‐1β, TNFα, iNOS, COX2, TLR4, IL‐6, MCP‐1, ICAM and CD40 were increased in the stromal cell fraction associated with visceral fat from pigs consuming high fat diets. No significant main effect of fat source was detected in visceral or peripheral fat stromal fraction. Interestingly, hippocampal gene expression of TLR4, TNFα and MCP‐1 and serum endotoxin was lower in AMF groups showing main effect of fat source. Overall, this study showed that diet containing AMF attenuated inflammatory parameters in serum, liver and, brain compared with diet of PO in juvenile pigs.Grant Funding Source: Supported by DRI #1101
Effect of providing a micronutrient‐fortified corn/soy atole or milk powder on linear growth in young Guatemalan children (828.6)
Authors: Villanueva Lisa , de Ponce Silvia , Alfonso Victor , Reinhart Gregory 
Published: June 2021

A community‐based feeding study was undertaken in Retalhuleu among 939 malnourished 6‐72 mo old children (HAZ <‐1). Children resided in 18 villages in an impoverished region of southwest Guatemala. Children were randomly assigned to two groups to compare effects of two nutritional interventions on growth and micronutrient status. Group A (n=667) children received 18.75 g of Chispuditos®, a corn/soy atole fortified with 21 vitamins and minerals (delivering 12.5 mg of iron and 9 mg of zinc per day). Group B (n=272) children received an equivalent portion by weight of lactose free milk (diets were isocaloric and isonitrogenous). At the conclusion of 12 mo, the average HAZ score of Group A children increased 12.0% from ‐2.76 to ‐2.43 (p<.01) and by 7.3%, from ‐2.87 to ‐2.66 (p<0.01) in Group B. Children from both dietary groups exhibited improvements in linear growth, with Group A having a greater increase in HAZ than Group B (p=0.01). Formative research conducted with the micronutrient‐fortified corn/soy atole revealed the product was well accepted by both primary caretakers and children. During the study time period Chispuditos was one‐third the cost of lactose free milk and provided a greater linear growth benefit. In conclusion, Chispuditos® is a culturally accepted, fortified atole that improves the health and nutritional status of children from 6‐72 mo of age in a more cost‐efficient manner compared to milk powder.Grant Funding Source: The Mathile Institute for the Advancement of Human Nutrition®
Estrogen compromises the facilitatory effect of chronic nicotine on adenosine A2B receptor/K+ channel‐mediated renal vasodilations (837.3)
Authors: El‐Mas Mahmoud , El‐Gowilly Sahar , Elsalakawy Lamia , El‐Gowelli Hanan 
Published: June 2021

We previously showed that the renal vasodilatory action of the adenosine analog 5’‐N‐ethyl carboxamidoadenosine (NECA) in female rats is mediated via adenosine A2B receptors (A2BRs) and is facilitated by estrogen (E2). We tested the hypothesis that renal NECA vasodilation and its estrogen and A2BR specificities are altered by chronic nicotine. Cumulative NECA (1.6–50 nmol) or papaverine (1‐243 nmol) vasodilations were not affected by nicotine (1‐8 mg/kg/day i.p., 2 weeks) in isolated phenylephrine‐preconstricted perfused kidneys of sham preparations. NECA, but not papaverine, vasodilations were reduced in kidneys of ovariectomized (OVX) rats and restored to near‐sham values after E2 replacement. Further, nicotine increased NECA vasodilations in OVX preparations in contrast to no effect in sham or OVXE2 kidneys. The enhanced NECA responsiveness in nicotine‐treated OVX preparations was abolished after the infusion of alloxazine (A2BR antagonist) or BaCl2 plus glibenclamide (blockers of inward rectifier and ATP‐sensitive K+ channels, respectively). Moreover, vasodilations caused by minoxidil (K+‐channel opener) were increased by nicotine in OVX, but not sham or OVXE2, preparations and this increase was abolished after BaCl2/glibenclamide infusion. Together, estrogen compromises the enhancing effect of nicotine on renal vasodilations evoked via the activation of the A2BR/K+ channel cascade.Grant Funding Source: Supported by STDF ID 502, Egypt
Evidence for ETB receptor regulation of circadian control of sodium excretion (860.1)
Authors: Johnston Jermaine , Speed Joshua , Pollock David 
Published: June 2021

Lack of renal ETB receptor function exacerbates circadian blood pressure variation in response to a high salt intake. Thus, we hypothesized that ET‐1 maintains normal circadian variation of sodium and water excretion through activation of the ETB receptor. To test this hypothesis, Sprague Dawley (SD) or ETB receptor deficient (sl/sl) rats were given a 900 μEq Na salt load by oral gavage at the beginning of either their active (dark) or inactive (light) cycle (7 pm or 7 am). Urine was collected in 12 hr increments and mean arterial pressure (MAP) measured by telemetry throughout the study. SD rats excreted the salt load during the initial 12 hrs whether given before their active (941 ± 88 baseline active period vs. 1548 ± 76 μEq Na/12 hr active period post gavage) or inactive cycle (362 ± 33 baseline vs. 944 ± 57 μEq Na/12 hr post gavage). Sl/sl rats also excreted the salt load when challenged during their active cycle (609 ± 25 baseline vs. 1119 ± 97 μEq Na/12 hr post gavage). However, sl/sl rats retained the salt load in the first 12 hr post gavage when given prior to the inactive period (364 ± 53 baseline vs. 464 ± 83 μEq Na/12 hr post gavage), but then excreted the salt load during the subsequent active period (684 ± 88 baseline vs. 1342 ± 121 μEq Na/12 hr, 24 hrs post gavage) and was associated with a significant elevation in MAP. These data demonstrate that the ETB receptor contributes to the circadian control of sodium excretion and blood pressure.Grant Funding Source: Supported by NIH grant P01 HL095499
Long‐term high salt diet delays development of renal injury and inflammation in murine systemic lupus erythematosus (860.12)
Authors: Broome Hanna , Ryan Michael 
Published: June 2021

Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent renal disease, for reasons that continue to be elucidated. Recent evidence suggests that dietary salt may be an important environmental factor that promotes some autoimmune diseases. Therefore, we hypothesized that a long‐term high salt diet would accelerate the progression of renal disease during SLE. In order to test this, an established experimental model of SLE (female NZBWF1 mice) was fed a standard (0.4% NaCl) or high salt (4% NaCl) diet starting at 10 weeks of age. Sodium intake (in meq/day) was measured three times throughout the study and was significantly greater in high salt fed animals at 16 weeks of age (2.9±0.6 vs. 0.5±0.06 , p=0.01), 23 weeks (4.8±0.8 vs. 0.6±0.06, p=0.004) and 29 weeks (5.7±0.6 vs. 0.6±0.05, p=0.0007). Urinary albumin was monitored monthly until 30 weeks then weekly by dipstick assay as a marker of renal injury until 34 weeks of age at which time the mice were euthanized and the kidneys were harvested. Renal cortex enriched mRNA was analyzed by qRT‐PCR for inflammatory markers. 80% of animals (n=5) on a normal diet developed albuminuria (蠅 100 mg/dL), whereas none (0%, n=5) of the high salt fed animals developed albuminuria. Renal cortical interleukin‐2 (IL‐2), a cytokine important for T cell differentiation, expression was significantly lower in high salt fed animals (0.26±0.14 relative to normal chow fed mice, p=0.03). These data suggest that, contrary to the original hypothesis, a long‐term high salt diet may protect against the renal injury associated with SLE, possibly through alterations in IL‐2 mediated T cell differentiation. Furthermore, the data advance our overall understanding of how dietary salt may impact different autoimmune disorders.Grant Funding Source: Supported by T32HL105324, 12GRNT12060203, HL085907, and HL051971
Right ventricular function following left myocardial infarction in rats with and without heart failure (864.6)
Authors: Fernandes Aurélia , Moura Viviane , Siman Fabiana , Ribeiro Júnior Rogério , Dias Fernanda , Jorge Zoghaib , Vassallo Paula , Vassallo Dalton , Stefanon Ivanita 
Published: June 2021

It has been proposed that right ventricular function is an independent predictor of mortality and development of heart failure in patients with known left ventricle dysfunction following myocardial infarction (MI). This study was conducted to assess right ventricle (RV) contractility 8 weeks following MI in rats presenting a moderate to large infarct area. Myocardial infarction was induced in male Wistar rats to create transmural infarctions involving 40‐60% of the left ventricle surface. Infarct rats were divided in two groups: those that presented classical signs of heart failure (HF group) and those that did not (INF group), and these two groups were used to study isometric contraction in isolated RV strips. Inotropic responses in the RV strips were preserved in the INF group but were reduced in the HF group (3.75 mM Ca2+ treatment: Sham=163±18; INF=148±19; HF=68±11 g/mg*; *p<0.05); (5x10‐5 M Isoproterenol treatment: Sham=151±15, INF=134±17, HF=52±7 g/mg*; *p<0.05). The infarcted group without signs of HF showed preserved contractility in RV strips in response to post‐rest potentiation, increases in extracellular Ca2+ and isoproterenol treatment. Indeed, SERCA‐2a protein expression was increased in the INF group but not in the HF group. In conclusion, increased SERCA‐2a protein expression may play a role in the preservation of RV function post‐MI. Therefore, therapeutic strategies that attempt to increase SERCA‐2a protein expression levels may be useful for the treatment of HF.Grant Funding Source: Supported by FAPES and CNPq
Murine airway slowly‐adapting receptor responses to lung inflation: a role for serotonin? (879.19)
Authors: Domnik Nicolle , Vincent Sandra , Cutz Ernest , Fisher John 
Published: June 2021

The mechanical phenotype of murine airway slowly‐adapting receptors (SARs), which are mechanosensitive afferents physiologically characterized by maintained discharge to sustained transmural pressure, is only partially defined. Adriaensen et al. suggest that densely‐innervated pulmonary neuroepithelial bodies (NEBs) are a morphological equivalent of SARs (Adriaensen et al. 2006, J Appl Physiol). Since NEBs release serotonin (5‐HT) in response to stretch in vitro (Pan et al. 2006, Am J Physiol Lung Cell Mol Biol), we characterized the mechanosensitivity of SARs during quasi‐static inflation to 20 cmH2O in male C57BL/6 mice and tested the impact of 5‐HT3 receptor blockade (i.v. tropisetron, Trop; 4.5mg/kg). SAR (n=8) discharge frequency (f; impulses/s) mechanosensitivity was proportional to tracheal pressure. Trop caused a small (3‐8%) but significant decrease in f vs. control (P=0.005; 2‐way ANOVA‐RM; mean±SEM (imp/s): 5cmH2O ‐ con: 91±13, Trop: 87±13; 10cmH2O ‐ con: 153±25, Trop: 143±22; 15cmH2O ‐ con: 192±29, Trop: 180±28; 20cmH2O ‐ con: 176±14, Trop: 164±15). It remains to be seen whether such a modest reduction in SAR discharge has a physiologic impact on the reflex effects of SAR medullary input.Grant Funding Source: Supported by: CIHR (JTF; MOP81211) & NSERC PostGrad Scholarship (NJD)
Profound metabolic depression in the hypoxia‐tolerant naked mole rat (879.2)
Authors: Pamenter Matthew , Dzal Yvonne , Milsom William 
Published: June 2021

Naked mole rats (NMRs) are among the most hypoxia‐tolerant mammals identified. Metabolic depression is a common response to hypoxia and is associated with lowered body temperature and a reduced state of activity (e.g. torpor). Contrary to this, NMRs maintain body temperature and remain active during prolonged exposure to 3% O2. The physiological adaptations that enable NMRs to remain active and thrive in hypoxia are poorly understood and we asked whether hypoxia‐induced changes to metabolic, ventilatory, or cardiac homeostasis contribute to this tolerance. To examine this question we exposed NMRs to progressive hypoxic epochs of 21, 9, 7, 5, and 3% O2 and measured metabolic rate, physical activity, ventilation, cardiac work, and body temperature. We found that NMRs exhibited profound metabolic depression (> 85%) at hypoxic levels < 7% O2, while maintaining body temperature and physical activity. Ventilation and heart rate increased with hypoxia but at a lower O2 levels than in hypoxia‐intolerant animals. Metabolic depression was reversed by systemic injection of the adenosine receptor antagonist aminotheophylline. Following injection, exposure to 7% O2 became lethal to animals that previously tolerated 3% O2 without detriment. We conclude that the hypoxia‐tolerance of NMRs is dependent upon robust metabolic depression, which is mediated by a mechanism involving adenosine receptor activation.Grant Funding Source: NSERC
A computational‐experimental protocol for investigating the quantity and anatomical location of pre‐glomerular oxygen shunting (890.13)
Authors: Kar Saptarshi , Gardiner Bruce , Smith David , Evans Roger , Ngo Jennifer 
Published: June 2021

Determination of the magnitude and location of pre‐glomerular oxygen shunting is critical in understanding its role in renal hypoxia. Unfortunately, experimental studies have been unable to quantify the magnitude and location of pre‐glomerular oxygen shunting. Computational models could theoretically fill this void by providing quantitative information related to renal oxygen shunting. However, their use is limited by uncertainty in model parameters. In this study we show the benefits of integrating oxygen pulse experiments with computational models of oxygen transport to quantitatively analyze oxygen shunting. The method involves injecting an oxygen pulse of known shape into the renal artery and monitoring the oxygen concentration profile at the renal vein exit. The shape and timing of the venous oxygen elution curve indicates the magnitude and location of oxygen shunting along the renal vasculature. Here, we developed a transient computational model for oxygen transport in pre‐glomerular vasculature simulating the above experimental protocol. The role of shunting on renal vascular oxygen transport is investigated by varying the shape of the input oxygen pulse in the renal artery and recording the timing and shapes of the corresponding exit pulses in the renal vein. The oxygen shunting parameters in our model can subsequently be fine‐tuned to match the pulse shapes from experimental data. The fine‐tuned model can then provide definitive answers about the magnitude and location of oxygen shunting.Grant Funding Source: NHMRC Australia Grant # 384101 and 606601
Differential effects of chemotherapeutic agents used to treat multiple myeloma on viability of colon cancer and colon cancer stem‐like cell lines (899.5)
Authors: Lenzi Kerry , Velez Hannah , Knabb Maureen 
Published: June 2021

Cancer stem cell (CSC) proliferation is one of the underlying causes for recurrence of malignancy. Chemotherapeutic agents used to treat multiple myeloma following stem cell transplant (SCT), such as lenalidomide (L) and bortezomib (B), are known to increase the risk of secondary cancers. Accordingly, the cytotoxic effects of L and B were investigated in human colon cancer HCT‐116 (C) and 5‐Fluorouracil/oxaliplatin (FOLFOX)‐resistant HCT cells. These FOLFOX‐resistant (R) cells are known to express CSC markers. Cells were cultured in DMEM with 10% FBS and cell growth inhibition was assessed using Dojindo CCK‐8 cell proliferation assay in 96‐well plates. In C cells, FOLFOX inhibited growth by 50% at a dose of 50 µM 5‐Fluorouracil + 1.25 µM oxaliplatin. A 500‐fold dose was required to inhibit growth by 50% in R cells. C cells were highly sensitive to B with an LD50 of 12 nM, but R cells remained viable at a 100 µM dose. L failed to induce cytotoxic effects in R and C cell lines. A higher sensitivity of colon cancer cells to bortezomib indicates that this would be the more efficacious maintenance therapy following stem cell transplant in MM patients. However, as evidenced by CSC resistance to bortezomib and lenalidomide, patients treated with these chemotherapeutic agents may be at risk for increased incidence of secondary cancer growth following SCT.Grant Funding Source: supported by WCU CASSDA award
Iron deficient toxic milk leads to the mask phenotype in hephaestin knockout mice (907.4)
Authors: Page Kathryn , Lachenauer Erica , Luong Julie , Han Chenchen , Irimagawa Hiroko , He Yuanchi , Killilea David , Frazer David , Anderson Gregory , Fuqua Brie , Vulpe Chris 
Published: June 2021

Iron is an essential element that is required for many cellular functions. Multiple symptoms of iron deficiency have been reported in humans, including anemia, hair loss, stunted growth, and reduced oxygen transport. Mammalian iron intake is mediated in two different ways, across the placenta during fetal growth, and through the intestine during postnatal growth and development. We previously identified hephaestin (Hp), a copper‐iron ferroxidase, which plays a key role in intestinal iron transport. Hephaestin oxidizes iron and works in conjunction with ferroportin to facilitate iron export from enterocytes and its efficient binding to plasma transferrin. Null mutations in the Hp gene cause an accumulation of intracellular iron, specifically in the intestine. During analysis of the Hp null mice, we discovered that neonates born to Hp knockout (Hp KO) dams developed truncal hair loss (the “mask” hair loss phenotype) that resolved after weaning. The same phenotype was also observed in pups born to mothers with intestine‐specific knockout of Hp (even WT (floxed) pups born to these mothers), suggesting that lack of maternal Hp in the intestine alone is responsible for the mask phenotype. In order to determine the stage (ante and/or post natal) at which lack of maternal Hp leads to pup hair loss, we performed cross‐fostering studies. Wild‐type pups fed by Hp KO dams presented with the “mask” phenotype, whereas, all pups fed by the WT dams had normal hair growth. Histology of the affected skin of pups fed by Hp KO dams showed disorientation and keratinization of the follicles, follicular infundibular plugging and some tortuosity to the hair canals. Our findings suggest the involvement of a “toxic milk” phenotype involving low iron levels in the milk causing this phenotype.Grant Funding Source: R01 GM083198‐01A1
Stretchy nerves withstand deformation associated with lunge feeding in rorqual whales (918.21)
Authors: Vogl A. , Lillie Margo , Piscitelli Marina , Shadwick Robert 
Published: June 2021

Rorqual whales have evolved a remarkable feeding strategy that involves rapidly gulping enormous quantities of prey‐laden water and then more slowly separating the prey from the water by filtering the material through baleen plates suspended from the roof of the oral cavity. During the initial engulfment, the tongue inverts into a ventral pouch and balloons backwards as far as the umbilicus. Simultaneously muscles in the floor of the oral cavity, and the overlying ventral groove blubber, dramatically expand to accommodate the engulfed water that can reach a volume exceeding that of the whale itself. We have found that large nerves in the tongue and in the floor of the oral cavity of adult fin whales can stretch or extend up to twice their initial lengths. This contrasts with intercostal nerves that are virtually inextensible. Histological analysis demonstrates that nerves in the tongue and floor of the oral cavity are surrounded by a very thick connective tissue coating consisting of elastin and collagen, and that the central nerve bundle itself is folded or coiled into a small central core ‐ not unlike a coiled string inside a much thicker bunge‐cord. Intercostal nerves are not folded and have much thinner surrounding walls. Stretchy nerves are yet another extreme morphological adaptation to lunge feeding in rorqual whales.Grant Funding Source: Supported by NSERC Discovery Grants