bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactide polymerization with iron alkoxide complexes
Authors: Keuchguerian Arek , Mougang-Soume Berline , Schaper Frank , Zargarian Davit
Published: February 2015

This report presents the results of a study on the preparation of iron alkoxide complexes chelated by diiminopyridine ligands and their role in the room temperature polymerization of rac-lactide. Reaction of N,N′-(p-R-C6H4CH2)2-diiminopyridines (R = H (1), F (2)) with FeX2 (X = Cl, Br) yielded the homoleptic complexes [(1)2Fe][FeX4] or [(2)2Fe][FeX4], respectively. Treating the latter with Na[BPh4] afforded the anion exchange product [(2)2Fe][BPh4]2, which was characterized by 1H NMR and absorption spectroscopy, combustion analysis, and single crystal X-ray diffraction. Various attempts to grow crystals of [(1)2Fe][FeX4] and [(2)2Fe][FeX4] culminated in the isolation of single crystals of [(2)2Fe][Cl6Fe2O] that was characterized by X-ray diffraction. Attempted synthesis of well-defined, mononuclear alkoxide derivatives from [(1)2Fe]2+ or [(2)2Fe]2+ gave mostly intractable products, but in one case we obtained the crystallographically characterized sodium iron cluster Na4Fe2(OC6H4F)8(THF)2. An aryloxide derivative proved accessible by reaction of NaOC6H4F with the mono-ligand precursor LFeCl2 (L = N,N′-dimesityl-diiminopyridine), but characterization of LFe(OC6H4F)2 was limited to a single crystal X-ray diffraction analysis, owing to unsuccessful attempts at isolating pure samples. The difficulties encountered in the isolation of pure alkoxide derivatives prompted us to use in-situ generated LFe(OEt)2 for studying the polymerization of rac-lactide. This system was found to be moderately active at room temperature and with a slight preference for the formation of a heterotactic polymer (Pr = 0.54–0.65). Large polydispersities of 1.5–2.0 indicated the presence of transesterification side-reactions, which were confirmed by the presence of peaks with m/z = n 144 + M(EtOH) + M(Na+) and m/z = (n + 0.5) 144 + M(EtOH) + M(Na+) in MALDI-MS.
Hydrodynamic control of benthic mats of Didymosphenia geminata at the reach scale
Authors: Cullis James Duncan Sydney , McKnight Diane Marie , Spaulding Sarah A.
Published: February 2015

Algal blooms caused by the stalk-forming diatom Didymosphenia geminata impact the habitat structure and functioning of stream ecosystems. We evaluated site-specific geomorphic controls on D. geminata in a cobble bed river in the Front Range of the Rocky Mountains. Entrainment potential, defined as the ratio of mean bed shear stress to the critical shear stress, was found to be the most important control on total abundance. A comparison with critical thresholds for sediment transport showed that the requirements for flushing flows to control D. geminata blooms are similar to that required for channel maintenance. Environmental parameters influencing the morphology of the algal mats and the potential for D. geminata to dominate the benthic algal community were also investigated. The results not only contribute to understanding of the controls on benthic algal growth in dynamic streams but also for management of water releases as mitigation for the control of future blooms of D. geminata.
The influence of prefire tree growth and crown condition on postfire mortality of sugar pine following prescribed fire in Sequoia National Park
Authors: Nesmith Jonathan C.B. , Das Adrian J. , O’Hara Kevin L. , van Mantgem Phillip J.
Published: February 2015

Tree mortality is a vital component of forest management in the context of prescribed fires; however, few studies have examined the effect of prefire tree health on postfire mortality. This is especially relevant for sugar pine (Pinus lambertiana Douglas), a species experiencing population declines due to a suite of anthropogenic factors. Using data from an old-growth mixed-conifer forest in Sequoia National Park, we evaluated the effects of fire, tree size, prefire radial growth, and crown condition on postfire mortality. Models based only on tree size and measures of fire damage were compared with models that included tree size, fire damage, and prefire tree health (e.g., measures of prefire tree radial growth or crown condition). Immediately following the fire, the inclusion of different metrics of prefire tree health produced variable improvements over the models that included only tree size and measures of fire damage, as models that included measures of crown condition performed better than fire-only models, but models that included measures of prefire radial growth did not perform better. However, 5 years following the fire, sugar pine mortality was best predicted by models that included measures of both fire damage and prefire tree health, specifically, diameter at breast height (DBH, 1.37 m), crown scorch, 30-year mean growth, and the number of sharp declines in growth over a 30-year period. This suggests that factors that influence prefire tree health (e.g., drought, competition, pathogens, etc.) may partially determine postfire mortality, especially when accounting for delayed mortality following fire.
Thin film flow of Casson liquid over a nonlinear stretching sheet in the presence of a uniform transverse magnetic field
Authors: Singh S.K. , Dandapat B.S.
Published: February 2015

Thin film flow of Casson liquid over a nonlinear stretching sheet is studied in the presence of a transverse uniform magnetic field. The evolution equation for the film thickness is derived using the long-wave approximation for thin liquid film and this nonlinear partial differential equation is solved numerically by using the Newton–Kantorovich method. Four different types of nonlinear stretching velocities are considered to study the effects of Casson parameter and Hartmann number on film thinning rate and the corresponding film thinning patterns are analyzed. It is observed that the Casson parameter exerts resistance on film thinning. Further it is also found that all types of stretching generate film thinning, but non-monotonic stretching provides faster thinning at small distances from the origin.
Begging form and growth pattern of nestlings correlate with parental food-allocation patterns in the Horned Lark (Eremophilaalpestris)
Authors: Du Bo , Liu Chang-Jing , Bao Shi-Jie
Published: February 2015

Life-history theory assumes that selection favors parents that can maximize their reproductive success via behavioral strategies. As brood size determines the reproductive value of each nestling, parents may adjust their food-allocation patterns according to brood size. We test this assumption in the Horned Lark (Eremophila alpestris (L., 1758)). Our findings revealed that nestling begging forms varied with brood size, by gaping in one-chick broods and postural activity in two- and three-chick broods. Accordingly, parental food-allocation patterns differed in different-sized broods. In one-chick broods, parents increased feeding rates with the gaping duration of nestling. In two-chick broods, parents did not change food-allocation patterns according to nestlings’ begging. In three-chick broods, however, they fed later-hatched nestlings more even when early-hatched nestlings begged more intensely. Horned Larks exhibited obvious sexual differences in parenting style and ability, which resulted in nestlings from two- and three-chick broods changing their begging intensity according to the sex of the provisioning adult. Furthermore, nestling growth pattern diverged with brood sizes, with body mass growing faster in one-chick broods than in two- and three-chick broods. Growth rate of beak gape and tarsus length did not differ significantly among brood sizes, but beak gape was larger and tarsus length was shorter in one-chick broods than in larger broods at fledging. Our results thus support the idea that parents may use food allocation to regulate sibling rivalry, which in turn cause nestlings to beg food in different forms and grow in different patterns so that their reproductive success can be enhanced.
Investigation of cues used by predators to detect Snapping Turtle (Chelydraserpentina) nests
Authors: Oddie Melissa A.Y. , Coombes Suzanne M. , Davy Christina M.
Published: February 2015

Nest predation is the leading cause of reproductive mortality in oviparous tetrapods and can limit population growth in some species. Rates of nest predation could be influenced through modification of the cues used to find nests, but this requires a clear understanding of how nests are located. Here, we used a buffet-style choice experiment to test the relative role of three cue types (visual, tactile, and chemosensory) on the detection and depredation of Snapping Turtle (Chelydra serpentina (L., 1758)) nests by a suite of predators dominated by raccoons (Procyon lotor (L., 1758)). We created sets of artificial nests along an authentic nesting site, presenting single or multiple cues. We interspersed artificial nests with authentic nests and monitored predation rates on both. Predators used all three cues to locate potential nests for investigation. However, nests with tactile cues were significantly more likely to be depredated than nests with only visual and chemosensory cues. Multiple cues had additive effects on predation probability. Addition of chemosensory cues to tactile treatments increased the probability of predation. The importance of tactile cues in this system supports the use of nest cages to protect nests in early stages of development, but cannot explain the recently described late-stage peak in predation.
On Gödel-type solution in Rastall's gravity
Authors: Santos A. F. , Ulhoa S. C.
Published: February 2015

Rastall's theory is a generalization of Einstein's equations in which the energy–momentum tensor is not a conserved quantity, its covariant derivative is proportional to the gradient of the Ricci scalar and this fact can be associated with quantum effects in curved spacetime. In this work we will go study the Rastall's gravity in the context of the Gödel-type universe.
Cholesteryl oleate-appended phthalocyanines as potential photosensitizers in the treatment of leishmaniasis
Authors: Contreras Laura E. Sánchez , Zirzlmeier Johannes , Kirner Sabrina V. , Setaro Francesca , Martínez Fernando , Lozada Stefany , Escobar Patricia , Hahn Uwe , Guldi Dirk M. , Torres Tomás
Published: February 2015

Two phthalocyanines (Pcs) with either a zinc or a ruthenium metal at the center of the macrocycle have been functionalized by a cholesteryl oleate moiety. The potential photosensitizers (PSs) for the treatment of cutaneous leishmaniasis have been studied on their photophysical properties and their ability to generate singlet oxygen. These experiments corroborate that solvent mixtures containing variable ratios of THF and water impact the excited state deactivation. The compounds were used preloaded into LDL particles and their phototoxic activity was evaluated in a preliminary way.
Undergraduates’ understanding of cardiovascular phenomena
Authors: Michael Joel A. , Wenderoth Mary Pat , Modell Harold I. , Cliff William , Horwitz Barbara , McHale Philip , Richardson Daniel , Silverthorn Dee , Williams Stephen , Whitescarver Shirley
Published: February 2015

Undergraduates students in 12 courses at 8 different institutions were surveyed to determine the prevalence of 13 different misconceptions (conceptual difficulties) about cardiovascular function. The prevalence of these misconceptions ranged from 20 to 81% and, for each misconception, was consistent across the different student populations. We also obtained explanations for the students’ answers either as free responses or with follow-up multiple-choice questions. These results suggest that students have a number of underlying conceptual difficulties about cardiovascular phenomena. One possible source of some misconceptions is the students’ inability to apply simple general models to specific cardiovascular phenomena. Some implications of these results for teachers of physiology are discussed.
STUDENT CRITICAL THINKING IS ENHANCED BY DEVELOPING EXERCISE PRESCRIPTIONS USING ONLINE LEARNING MODULES
Authors: Brahler C. Jayne , Quitadamo Ian J. , Johnson Emily C.
Published: February 2015

Developing the ability to think critically is an important element of undergraduate physiology education and is influenced by many factors, including the learning environment, the social context of the learning environment, and the instructor’s approach to teaching. In this work, we describe online learning modules (OLM) that were designed to promote higher-order critical thinking skills in students enrolled in an upper-division Exercise Testing and Prescription course. The OLM provided students with an online learning environment in which to review clinical physiological details from authentic patient case data and develop exercise prescriptions (ExRx), by requiring students to critically analyze authentic patient case histories and collaborate on computer-based learning activities. On the basis of assessment data, we conclude that the OLM helped exercise science students develop the critical thinking skills necessary for development of effective exercise prescriptions by requiring them to think critically while concurrently reinforcing lecture-presented exercise science content.
LABORATORY DEMONSTRATION OF BAROREFLEX CONTROL OF HEART RATE IN CONSCIOUS RATS
Authors: O’Donaughy Theresa L. , Resta Thomas C. , Walker Benjimen R.
Published: February 2015

We have developed a laboratory exercise that demonstrates arterial baroreflex control of heart rate (HR) in the conscious unrestrained rat, incorporating graduate level physiological topics as well as a hands-on exposure to conscious animal research. This demonstration utilizes rats chronically instrumented to measure cardiac output (CO), HR, and arterial blood pressure in response to agents that raise or lower blood pressure. The HR response to progressive increases or decreases in blood pressure is recorded, and a baroreflex curve is generated by plotting mean arterial blood pressure (MABP) vs. HR. Observation of altered CO allows for discussion of the relationship between MAP, CO, HR, stroke volume, and total peripheral resistance. Administration of arginine vasopressin demonstrates the ability of this hormone to alter the sensitivity of the baroreflex. Throughout the demonstration, students answer questions from a handout about general cardiovascular physiology, specific pathways of agonists, and the baroreflex system, encouraging group and individual critical analysis of the results. Interpretation of the data reemphasizes lecture material and allows students to observe the baroreflex response in a physiological setting.
Evaluation of a computer-based approach to teaching acid/base physiology
Authors: Rawson Richard E. , Quinlan Kathleen M.
Published: February 2015

Because acid/base physiology is a difficult subject for most medical and veterinary students, the first author designed a software program, Acid/Base Primer, that would help students with this topic. The Acid/Base Primer was designed and evaluated within a conceptual framework of basic educational principles. Seventy-five first-year veterinary students (of 81; 93% response rate) participated in this study. Students took both a pre- and posttest of content understanding. After completing the Acid/Base Primer in pairs, each student filled out a survey evaluating the features of the program and describing his/her use and experience of it. Four pairs of students participated in interviews that elaborated on the surveys. Scores improved from 53 ± 2% on the pretest to 74 ± 1% on an immediate posttest. On surveys and in interviews, students reported that the program helped them construct their own understanding of acid/base physiology and prompted discussions in pairs of students when individual understandings differed. The case-based format provided anchors and a high degree of relevance. Repetition of concepts helped students develop a more complex network of understanding. Questions in the program served to scaffold the learning process by providing direction, accentuating the relevant features of the cases, and provoking discussion. Guidelines for software development were generated on the basis of the findings and relevant educational literature.
GENE EXPRESSION STUDIES USING MICROARRAYS: PRINCIPLES, PROBLEMS, AND PROSPECTS
Authors: Murphy David
Published: February 2015

Anumber of mammalian genomes having been sequenced, an important next step is to catalog the expression patterns of all transcription units in health and disease by use of microarrays. Such discovery programs are crucial to our understanding of the gene networks that control developmental, physiological, and pathological processes. However, despite the excitement, the full promise of microarray technology has yet to be realized, as the superficial simplicity of the concept belies considerable problems. Microarray technology is very new; methodologies are still evolving, common standards have yet to be established, and many problems with experimental design and variability have still to be fully understood and overcome. This review will describe the time course of a microarray experiment—RNA isolation from sample, target preparation, hybridization to the microarray probe, data capture, and bioinformatic analysis. For each stage, the advantages and disadvantages of competing techniques are compared, and inherent sources of error are identified and discussed.
Insulinotropic activity of the imidazoline derivative RX871024 in the diabetic GK rat
Authors: Efanov Alexander M. , Appelskog Ioulia B. , Abdel-Halim Samy M. , Khan Akhtar , Bränström Robert , Larsson Olof , Östenson Claes-Göran , Mest Hans-Juergen , Berggren Per-Olof , Efendic Suad , Zaitsev Sergei V.
Published: February 2015

The insulinotropic activity of the imidazoline derivative RX871024 was compared in pancreatic islets from nondiabetic Wistar rats and spontaneously diabetic Goto-Kakizaki (GK) rats. RX871024 significantly stimulated insulin secretion in islets from both animal groups. The insulinotropic activity of RX871024 was higher than that of the sulfonylurea glibenclamide. This difference was more pronounced in islets from GK rats compared with Wistar rat islets. More importantly, RX871024 substantially improved glucose sensitivity in diabetic β-cells, whereas glibenclamide stimulated insulin secretion about twofold over a broad range of glucose concentrations in nondiabetic and diabetic rats. RX871024 induced a faster increase in cytosolic free Ca2+concentration and faster inhibition of ATP-dependent K+channel activity in GK rat islets compared with Wistar rat islets. RX871024 also induced a more pronounced increase in diacylglycerol concentration in GK rat islets. These data support the idea that imidazoline compounds can form the basis for the development of novel drugs for treatment of type 2 diabetes, which can restore glucose sensitivity in diabetic β-cells.
Enhancement of the inducible NO synthase activation by retinoic acid is mimicked by RARα agonist in vivo
Authors: Seguin-Devaux Carole , Devaux Yvan , Latger-Cannard Véronique , Grosjean Sandrine , Rochette-Egly Cécile , Zannad Faiez , Meistelman Claude , Mertes Paul-Michel , Longrois Dan
Published: February 2015

We have previously shown that all- trans retinoic acid (atRA), the active metabolite of vitamin A, enhances the activation of the inducible nitric oxide synthase (NOS II) pathway, a component of innate immunity, in rats in vivo. We investigated the relative contribution of retinoic acid receptor-α (RARα) and retinoid X receptors (RXRs) to NOS II activation triggered by LPS. Five-day supplementation with 10 mg/kg of either atRA or the RARα selective agonist Ro-40-6055, but not with 10 mg/kg of the pan-RXR agonist Ro-25-7386, enhanced the LPS-induced NOS II mRNA, protein expression in liver, and plasma nitrite/nitrate concentration. Both atRA and the RARα agonist (but not the RXR agonist) increased the number of peripheral T helper lymphocytes and plasma interferon-γ concentration. Synergism between retinoids and LPS on NOS II activation within an organ coincided with synergism on interferon regulatory factor-1 mRNA expression but not with the level of expression of the RARα protein. These results suggest that, in vivo, atRA activates NOS II through RARα and contributes to characterizing the complex effect of retinoids on the host inflammatory/immune response.
NH2terminus of PTB-associated splicing factor binds to the porcine P450scc IGF-I response element
Authors: Urban Randall J. , Bodenburg Yvonne H. , Wood Thomas G.
Published: February 2015

An insulin-like growth factor (IGF) I response element (IGFRE) in the porcine P-450 cholesterol side-chain cleavage gene (P450scc) regulates transcription through the binding of two proteins, Sp1 and polypyrimidine tract-binding protein-associated splicing factor (PSF). PSF is a component of spliceosomes and contains RNA-binding domains. In this study, we localized the NH2-terminal amino acid residues necessary for binding of PSF to the IGFRE. Three COOH-terminal truncated proteins (aa 304, 214, and 134) of PSF were designed to empirically partition the NH2-terminal region while excluding the RNA-binding domains. Southwestern analysis showed that only the largest expressed truncated protein, P3, strongly bound the porcine P450scc IGFRE. Truncated PSF protein expression in Y1 adrenal cells showed that P3 repressed transcriptional activity of the IGFRE similar to full-length PSF, whereas P2 (minimal binding to the IGFRE) had no effect. In conclusion, the NH2-terminal region of PSF contains the amino acid residues necessary for binding to the porcine P450scc IGFRE and repressing the transcriptional activity of the element.
Metabolic basis of HIV-lipodystrophy syndrome
Authors: Sekhar Rajagopal V. , Jahoor Farook , White A. Clinton , Pownall Henry J. , Visnegarwala Fehmida , Rodriguez-Barradas Maria C. , Sharma Morali , Reeds Peter J. , Balasubramanyam Ashok
Published: February 2015

Human immunodeficiency virus (HIV)-lipodystrophy syndrome (HLS) is characterized by hypertriglyceridemia, low high-density lipoprotein-cholesterol, lipoatrophy, and central adiposity. We investigated fasting lipid metabolism in six men with HLS and six non-HIV-infected controls. Compared with controls, HLS patients had lower fat mass (15.9 ± 1.3 vs. 22.3 ± 1.7 kg, P < 0.05) but higher plasma glycerol rate of appearance (Ra), an index of total lipolysis (964.71 ± 103.33 vs. 611.08 ± 63.38 μmol · kg fat−1· h−1, P < 0.05), Rapalmitate, an index of net lipolysis (731.49 ± 72.36 vs. 419.72 ± 33.78 μmol · kg fat−1· h−1, P < 0.01), Rafree fatty acids (2,094.74 ± 182.18 vs. 1,470.87 ± 202.80 μmol · kg fat−1· h−1, P < 0.05), and rates of intra-adipocyte (799.40 ± 157.69 vs. 362.36 ± 74.87 μmol · kg fat−1· h−1, P < 0.01) and intrahepatic fatty acid reesterification (1,352.08 ± 123.90 vs. 955.56 ± 124.09 μmol · kg fat−1· h−1, P < 0.05). Resting energy expenditure was increased in HLS patients (30.51 ± 2.53 vs. 25.34 ± 1.04 kcal · kg lean body mass−1· day−1, P < 0.05), associated with increased non-plasma-derived fatty acid oxidation (139.04 ± 24.17 vs. 47.87 ± 18.81 μmol · kg lean body mass−1· min−1, P < 0.02). The lipoatrophy observed in HIV lipodystrophy is associated with accelerated lipolysis. Increased hepatic reesterification promotes the hypertriglyceridemia observed in this syndrome.
EnhancedO-GlcNAc protein modification is associated with insulin resistance in GLUT1-overexpressing muscles
Authors: Buse Maria G. , Robinson Katherine A. , Marshall Bess A. , Hresko Richard C. , Mueckler Mike M.
Published: February 2015

O-linked glycosylation on Ser/Thr with single N-acetylglucosamine ( O-GlcNAcylation) is a reversible modification of many cytosolic/nuclear proteins, regulated in part by UDP-GlcNAc levels. Transgenic (T) mice that overexpress GLUT1 in muscle show increased basal muscle glucose transport that is resistant to insulin stimulation. Muscle UDP-GlcNAc levels are increased. To assess whether GLUT4 is a substrate for O-GlcNAcylation, we translated GLUT4 mRNA (mutated at the N-glycosylation site) in rabbit reticulocyte lysates supplemented with [35S]methionine. O-GlcNAcylated proteins were galactosylated and separated by lectin affinity chromatography; >20% of the translated GLUT4 appeared to be O-GlcNAcylated. To assess whether GLUT4 or GLUT4-associated proteins were O-GlcNAcylated in muscles, muscle membranes were prepared from T and control (C) mice labeled with UDP-[3H]galactose and immunoprecipitated with anti-GLUT4 IgG (or nonimmune serum), and N-glycosyl side chains were removed enzymatically. Upon SDS-PAGE, several bands showed consistently two- to threefold increased labeling in T vs. C. Separating galactosylated products by lectin chromatography similarly revealed approximately threefold more O-GlcNAc-modified proteins in T vs. C muscle membranes. RL-2 immunoblots confirmed these results. In conclusion, chronically increased glucose flux, which raises UDP-GlcNAc in muscle, results in enhanced O-GlcNAcylation of membrane proteins in vivo. These may include GLUT4 and/or GLUT4-associated proteins and may contribute to insulin resistance in this model.
Estrogen-induced osteogenesis in intact female mice lacking ERβ
Authors: McDougall K. E. , Perry M. J. , Gibson R. L. , Bright J. M. , Colley S. M. , Hodgin J. B. , Smithies O. , Tobias J. H.
Published: February 2015

We recently found that estrogen receptor (ER) antagonists prevent high-dose estrogen from inducing the formation of new cancellous bone within the medullary cavity of mouse long bones. In the present investigation, we studied the role of specific ER subtypes in this response by examining whether this is impaired in female ERβ−/− mice previously generated by targeted gene deletion. Vehicle or 17β-estradiol (E2) (range 4–4,000 μg · kg−1 · day−1) was administered to intact female ERβ−/− mice and wild-type littermates by subcutaneous injection for 28 days. The osteogenic response was subsequently assessed by histomorphometry performed on longitudinal and cross sections of the tibia. E2 was found to cause an equivalent increase in cancellous bone formation in ERβ−/− mice and littermate controls, as assessed at the proximal and distal regions of the proximal tibial metaphysis. E2 also resulted in a similar increase in endosteal mineral apposition rate in these two genotypes, as assessed at the tibial diaphysis. In contrast, cortical area in ERβ−/− mice was found to be greater than that in wild types irrespective of E2 treatment, as was tibial bone mineral density as measured by dual-energy X-ray absorptiometry, consistent with previous reports of increased cortical bone mass in these animals. We conclude that, although ERβ acts as a negative modulator of cortical modeling, this isoform does not appear to contribute to high-dose estrogen's ability to induce new cancellous bone formation in mouse long bones.
IGF-I promotes a shift in metabolic flux in vascular smooth muscle cells
Authors: Hall Jennifer L. , Gibbons Gary H. , Chatham John C.
Published: February 2015

13C-nuclear magnetic resonance (NMR) spectroscopy was used to test our hypothesis that insulin-like growth factor I (IGF-I) stimulates glucose flux into both nonoxidative and oxidative pathways in vascular smooth muscle cells (VSMC). Rat VSMC were exposed to uniformly labeled [13C]glucose ([U-13C]glucose; 5.5 mM) and [3-13C]pyruvate (1 mM) in the presence and absence of IGF-I (100 ng/ml). IGF-I increased glucose flux through glycolysis and the tricarboxylic acid (TCA) cycle as well as total anaplerotic flux into the TCA cycle. Previous work in our laboratory identified an increase in GLUT1 content and glucose metabolism in neointimal VSMC that was sufficient to promote proliferation and inhibit apoptosis. To test whether IGF-I could potentiate the GLUT1-induced increased flux in the neointima, we utilized VSMC harboring constitutive overexpression of GLUT1. Indeed, IGF-I markedly potentiated the GLUT1-induced increase in glucose flux through glycolysis and the TCA cycle. Taken together, these findings demonstrate that upregulation of glucose transport through either IGF-I or increased GLUT1 content stimulates glucose flux through both nonoxidative and oxidative pathways in VSMC.
Characterization of the portal signal in a nonsteady hyperglycemic state in conscious dogs
Authors: Ogihara N. , Ebihara S. , Kawamura W. , Okamoto M. , Sakai T. , Takiguchi K. , Morita T. , Uchida R. , Matsuyama Y. , Hayashi Y. , Arakawa Y. , Kikuchi M.
Published: February 2015

To characterize the “portal signal” in a nonsteady hyperglycemic state, the kinetic relationship between net hepatic glucose balance (NHGB) and either hepatic glucose load (HGL) or plasma insulin level was determined during glucose infusion using a catheter technique in 36 conscious dogs. Glucose was infused intraportally (Po group) and peripherally (Pe group) at 39, 56, and 83 μmol · kg−1 · min−1over 2 h. There was a linear relationship between mean NHGB and either mean HGL or plasma insulin levels at each rate in either delivery (HGL: Po r = 0.99, Pe r = 0.95; insulin: Po r = 99, Pe r = 0.79). The threshold levels for net hepatic glucose uptake were 3.8 and 11.7 mmol/l for plasma glucose and 65 and 392 pmol/l for plasma insulin, respectively. The slope of the regression line against the abscissa was four times larger in portal than in peripheral delivery (HGL: Po 0.20 vs. Pe 0.05, P < 0.05; insulin: Po 0.19 vs. Pe 0.04, P < 0.05). These results suggest that the portal signal overrules the threshold of glucose for hepatic uptake by increasing hepatic extraction rate in a nonsteady hyperglycemic state.
Acute IGF-I infusion stimulates protein synthesis in skeletal muscle and other tissues of neonatal pigs
Authors: Davis Teresa A. , Fiorotto Marta L. , Burrin Douglas G. , Vann Rhonda C. , Reeds Peter J. , Nguyen Hanh V. , Beckett Philip R. , Bush Jill A.
Published: February 2015

Studies have shown that protein synthesis in skeletal muscle of neonatal pigs is uniquely sensitive to a physiological rise in both insulin and amino acids. Protein synthesis in cardiac muscle, skin, and spleen is responsive to insulin but not amino acid stimulation, whereas in the liver, protein synthesis responds to amino acids but not insulin. To determine the response of protein synthesis to insulin-like growth factor I (IGF-I) in this model, overnight-fasted 7- and 26-day-old pigs were infused with IGF-I (0, 20, or 50 μg · kg−1 · h−1) to achieve levels within the physiological range, while amino acids and glucose were clamped at fasting levels. Because IGF-I infusion lowers circulating insulin levels, an additional group of high-dose IGF-I-infused pigs was also provided replacement insulin (10 ng · kg−0.66 · min−1). Tissue protein synthesis was measured using a flooding dose ofl-[4-3H]phenylalanine. In 7-day-old pigs, low-dose IGF-I increased protein synthesis by 25–60% in various skeletal muscles as well as in cardiac muscle (+38%), skin (+24%), and spleen (+32%). The higher dose of IGF-I elicited no further increase in protein synthesis above that found with the low IGF-I dose. Insulin replacement did not alter the response of protein synthesis to IGF-I in any tissue. The IGF-I-induced increases in tissue protein synthesis decreased with development. IGF-I infusion, with or without insulin replacement, had no effect on protein synthesis in liver, jejunum, pancreas, or kidney. Thus the magnitude, tissue specificity, and developmental change in the response of protein synthesis to acute physiological increases in plasma IGF-I are similar to those previously observed for insulin. This study provides in vivo data indicating that circulating IGF-I and insulin act on the same signaling components to stimulate protein synthesis and that this response is highly sensitive to stimulation in skeletal muscle of the neonate.
Insulin signaling during perinatal liver development in the rat
Authors: Anand Padmanabhan , Boylan Joan M. , Ou Yangsi , Gruppuso Philip A.
Published: February 2015

Insulin has long been assigned a key role in the regulation of growth and metabolism during fetal life. Our prior observations indicated that hepatic insulin signaling is attenuated in the late-gestation fetal rat. Therefore, we studied the perinatal ontogeny of hepatic insulin signaling extending from phosphatidylinositol 3-kinase (PI3K) to the ribosome. Initial studies demonstrated markedly decreased insulin-mediated activation of ribosomal protein S6 kinase 1 (S6K1) in the fetus. We found a similar pattern in the regulation of Akt, a kinase upstream from S6K1. Insulin produced minimal activation of insulin receptor substrate (IRS)-1-associated PI3K activity in fetal liver. A modest IRS-2-associated response was seen in the fetus. However, levels of both IRS-1 and IRS-2 were very low in fetal liver relative to adult liver. IRS-1 content and insulin responsiveness of PI3K, Akt, and S6K1 showed a transition to the adult phenotype during the first several postnatal weeks. Examination of downstream insulin signaling to the translational apparatus showed marked attenuation, relative to the adult, of fetal hepatic insulin-mediated phosphorylation of 4E-BP1, the regulatory protein for the eukaryotic initiation factor eIF4E, and ribosomal protein S6. The mammalian target of rapamycin (mTOR), a key integrator of nutritional and metabolic regulation of translation, was present in low amounts, was hypophosphorylated, and was not insulin sensitive in the fetus. Our results indicate that protein synthesis during late-gestation liver development may be mTOR and insulin independent. Reexamination of the role of insulin in fetal liver physiology may be warranted.
Ceramides and sphingomyelins in skeletal muscles of the rat: content and composition. Effect of prolonged exercise
Authors: Dobrzyń Agnieszka , Górski Jan
Published: February 2015

The sphingomyelin-signaling pathway has been described in many tissues. Ceramide is the main second messenger in this pathway. Ceramide has also been shown to be present in skeletal muscles; however, there are few data on the regulation of the content of ceramide in muscle tissue. Moreover, there are no data on the content of particular ceramides or their composition in the muscles. The aim of the present study was to examine the content and composition of fatty acids (FA) in ceramide and sphingomyelin moieties and the activity of neutral Mg2+-dependent sphingomyelinase in different skeletal muscle types of the rat at rest and after exhausting exercise of moderate intensity. The experiments were carried out on male Wistar rats, divided into two groups: 1) control and 2) exercised until exhaustion on a treadmill. Soleus and red and white gastrocnemius muscles were taken. Ceramide and sphingomyelin were separated by TLC. The content of individual FA in the two compounds was determined by gas-liquid chromatography. Twelve different ceramides and sphingomyelins were identified and quantified in each muscle type according to the FA residues. Saturated FA consisted of 68, 67, and 66% of total ceramide-FA and 75, 77, and 78% of total sphingomyelin-FA in soleus and red and white gastrocnemius, respectively. The total content of ceramide- and sphingomyelin-FA and the activity of sphingomyelinase were highest in the soleus and lowest in the white gastrocnemius. Exercise resulted in a reduction in the total content of ceramide- and sphingomyelin-FA in each muscle. This was accounted for mostly by a reduction in content in the amount of saturated FA. Exercise reduced the activity of neutral Mg2+-dependent sphingomyelinase in the soleus and red gastrocnemius and did not affect its activity in the white gastrocnemius. We conclude that the sphingomyelin-signaling pathway is present in skeletal muscles and that it is influenced by prolonged exercise.
Multiple forms of estrogen receptor-α in cerebral blood vessels: regulation by estrogen
Authors: Stirone Chris , Duckles Sue P. , Krause Diana N.
Published: February 2015

The cerebral vasculature is an important target tissue for estrogen, as evidenced by significant effects of estrogen on vascular reactivity and protein levels of endothelial nitric oxide synthase and prostacyclin synthase. However, the presence, localization, and regulation of estrogen receptors in the cerebral vasculature have not been investigated. In this study, we identified the presence of estrogen receptor-α (ER-α) in female rat cerebral blood vessels and localized this receptor to both smooth muscle and endothelial cells by use of immunohistochemistry and confocal microscopy. With immunoblot analysis, multiple forms of ER-α were detected at 110, 93, 82, 50, and 45 kDa in addition to a relatively weak band corresponding to the 66-kDa putative unmodified receptor. The 82-kDa band was identified as Ser118-phosphorylated ER-α, whereas the 50-kDa band lacks the normal NH2terminus, suggestive of an ER-α splice variant. Lower molecular mass bands persisted after in vivo inhibition of 26S proteasome activity with lactacystin, whereas the 110- and 93-kDa bands increased. All forms of ER-α in cerebral vessels were decreased after ovariectomy but significantly increased after chronic estrogen exposure in vivo.
PTB-associated splicing factor regulates growth factor-stimulated gene expression in mammalian cells
Authors: Urban Randall J. , Bodenburg Yvonne
Published: February 2015

An insulin-like growth factor I (IGF-I) response element (IGFRE) in the porcine P-450 cholesterol side-chain cleavage gene (P450scc) binds two transcription factors, Sp1 and polypyrimidine tract-binding protein-associated splicing factor (PSF). In this study, we investigated expression of these transcription factors in mouse Y1 adrenal cells, a cell line that does not increase P450scc expression in response to IGF-I. Western blot analysis showed a greater expression of PSF in Y1 cells when compared with a mouse fibroblast cell line (NWTb3) in which IGF-I stimulates the P450scc IGFRE. The two cell lines expressed Sp1 equally, and IGF-I did not increase expression of either transcription factor. Chromatin immunoprecipitation analysis with Y1 chromatin confirmed that PSF and Sp1 bound to the IGFRE. When increasing amounts of Sp1 were expressed in Y1 cells, the IGFRE became responsive to IGF-I. Moreover, a mutant oligonucleotide IGFRE reporter construct that lacks PSF binding was responsive to IGF-I. In conclusion, Y1 adrenal cells are a physiological example of PSF repression of growth factor-stimulated (IGF-I) gene expression (P450scc). The dynamic nature of this repression is consistent with PSF functioning as a regulator of growth factor-stimulated gene expression in mammalian cells.
Metabolic effects of nandrolone decanoate and resistance training in men with HIV
Authors: Sattler Fred R. , Schroeder E. Todd , Dube Michael P. , Jaque S. Victoria , Martinez Carmen , Blanche Patricia J. , Azen Stanley , Krauss Ronald M.
Published: February 2015

Thirty human immunodeficiency virus (HIV)-infected men were randomized to a high dose of nandrolone decanoate weekly ( group 1) or nandrolone plus resistance training ( group 2) for 12 wk. For the two groups, nandrolone had no significant effects on total cholesterol, LDL cholesterol, LDL phenotype, or fasting triglycerides, although triglycerides decreased by 66 ± 124 mg/dl for the entire population ( P = 0.01). Group 2 subjects had a favorable increase of 5.2 ± 7.7Å in LDL particle size ( P = 0.03), whereas there was no change in group 1. Lipoprotein(a) decreased by 7.3 ± 6.8 mg/dl for group 1 ( P = 0.002) and by 6.9 ± 8.1 for group 2 ( P= 0.013). However, HDL cholesterol decreased by 8.7 ± 7.4 mg/dl for group 1 ( P < 0.001) and by 10.6 ± 5.9 for group 2 ( P < 0.001). Percentages of HDL2b(9.7–12 nm) and HDL2a(8.8–9.7 nm) subfractions decreased similarly for the two groups, whereas HDL3a(8.2–8.8 nm) and HDL3b(7.8–8.2 nm) increased in the groups during study therapy ( P ≤ 0.02 for all comparisons). There was no evidence of a decreased insulin sensitivity in either group, whereas fasting glucose, fasting insulin, and homeostasis model assessment improved in group 2( P < 0.05). These metabolic effects were favorable (other than for HDL), but changes were generally transient (except for HDL in group 2), with measurements returning to baseline 2 mo after the interventions were completed.
Plasma l-5-oxoproline kinetics and whole blood glutathione synthesis rates in severely burned adult humans
Authors: Yu Yong-Ming , Ryan Colleen M. , Fei Zhe-Wei , Lu Xiao-Ming , Castillo Leticia , Schultz John T. , Tompkins Ronald G. , Young Vernon R.
Published: February 2015

Compromised glutathione homeostasis is associated with increased morbidity in various disease states. We evaluated the kinetics of l-5-oxoproline, an intermediate in the γ-glutamyl cycle of glutathione production, in fourteen severely burned adults by use of a primed, constant intravenous infusion of l-5-[1-13C]oxoproline. In nine of these patients, whole blood glutathione synthesis and plasma kinetics of glycine and leucine were also measured with [15N]glycine andl-[2H3]leucine tracers. Patients were studied under a “basal” condition that provided a low dose of glucose and total parenteral nutrition. For comparison with control subjects, whole blood glutathione synthesis was estimated in six healthy adults. Burn patients in a basal condition showed significantly higher rates of plasma oxoproline clearance and urinaryd- and l-oxoproline excretion compared with fasting healthy control subjects. Whole blood glutathione concentration and absolute synthesis rate in the basal state were lower than for control subjects. Total parenteral feeding without cysteine but with generous methionine did not affect oxoproline kinetics or whole blood glutathione synthesis. The estimated rate of glycine de novo synthesis was also lower in burn patients, suggesting a possible change in glycine availability for glutathione synthesis. The roles of precursor amino acid availability, as well as alterations in metabolic capacity, in modulating whole blood glutathione production in burns now require investigation.
Underestimation of gluconeogenesis by the [U-13C6]glucose method: effect of lack of isotope equilibrium
Authors: Mao Catherine S. , Bassilian Sara , Lim Shu K. , Lee W.-N. Paul
Published: February 2015

Among the many tracer methods to indirectly estimate gluconeogenesis in humans, the [U-13C6]glucose method as proposed by Tayek and Katz ( Am J Physiol Endocrinol Metab 270: E709–E717, 1996; Am J Physiol Endocrinol Metab272: E476–E484, 1997) has the advantage of being able to simultaneously estimate hepatic glucose output and fractional gluconeogenesis. However, Landau et al. (Landau BR, J Wahren, K Ekberg, SF Previs, D Yang, and H Brunengraber. Am J Physiol Endocrinol Metab 274: E954–E961, 1998) have shown that this method underestimates the rate of gluconeogenesis. The underestimation has been attributed to tracer dilution by other three-carbon substrates and the lack of isotopic steady state. Using a computer simulation of [U-13C6]glucose infusion, we demonstrate that the lack of isotope equilibrium in both the lactate and glucose compartments contributes substantially to the underestimation of gluconeogenesis. [U-13C6]glucose experiments were performed with the addition of a primed constant infusion of [U-13C3]lactate and the delay in M3 glucose equilibrium estimated from the isotopic steady-state value determined by modeling M3 glucose to a single-exponential fit. We found that, even with the addition of [U-13C3]lactate infusion, the M3 glucose enrichment of the last timed sample was ∼20% less than the isotopic steady-state value. Thus the lack of isotopic equilibrium of the glucose compartment potentially accounts for 20% of the underestimation of gluconeogenesis. The underestimation of gluconeogenesis using [U-13C6]glucose without the additional infusion of [U-13C3]lactate in previous publications is expected to be even greater because of the lack of isotope equilibrium in both the lactate and glucose compartments. These findings are consistent with the results from our computer simulation.
Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor, NPY, and AgRP mRNA expression
Authors: Wang Hongqin , Storlien Len H. , Huang Xu-Feng
Published: February 2015

Some, but not all, fats are obesogenic. The aim of the present studies was to investigate the effects of changing type and amount of dietary fats on energy balance, fat deposition, leptin, and leptin-related neural peptides: leptin receptor, neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC), in C57Bl/6J mice. One week of feeding with a highly saturated fat diet resulted in ∼50 and 20% reduction in hypothalamic arcuate NPY and AgRP mRNA levels, respectively, compared with a low-fat or an n-3 or n-6 polyunsaturated high-fat (PUFA) diet without change in energy intake, fat mass, plasma leptin levels, and leptin receptor or POMC mRNA. Similar neuropeptide results were seen at 7 wk, but by then epididymal fat mass and plasma leptin levels were significantly elevated in the saturated fat group compared with low-fat controls. In contrast, fat and leptin levels were reduced in the n-3 PUFA group compared with all other groups. At 7 wk, changing the saturated fat group to n-3 PUFA for 4 wk completely reversed the hyperleptinemia and increased adiposity and neuropeptide changes induced by saturated fat. Changing to a low-fat diet was much less effective. In summary, a highly saturated fat diet induces obesity without hyperphagia. A regulatory reduction in NPY and AgRP mRNA levels is unable to effectively counteract this obesogenic drive. Equally high fat diets emphasizing PUFAs may even protect against obesity.
Analysis of energy expenditure at different ambient temperatures in mice lacking DGAT1
Authors: Chen Hubert C. , Ladha Zuleika , Smith Steven J. , Farese Robert V.
Published: February 2015

Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in triglyceride synthesis, have increased energy expenditure and therefore are resistant to obesity. Because ambient temperature can significantly affect energy expenditure in mice, we undertook these studies to determine the effects of different ambient temperatures on energy expenditure, food intake, and thermoregulation in DGAT1-deficient [ Dgat1(−/−)] mice. Dgat1(−/−) mice had increased energy expenditure irrespective of changes in the ambient temperature. Although core temperature was normal, surface temperature was increased in Dgat1(−/−) mice, most likely reflecting an active mechanism to dissipate heat from increased thermogenesis. Dgat1(−/−) mice had increased food intake at baseline, and this hyperphagia became more pronounced upon exposure to cold. When fasted in a cold environment, Dgat1(−/−) mice developed hypothermia, which was associated with hypoglycemia. These results suggest that the hyperphagia in Dgat1(−/−) mice is a secondary mechanism that compensates for the increased utilization of fuel substrates. Our findings offer insights into the mechanisms of hyperphagia and increased energy expenditure in a murine model of obesity resistance.