bluuebunny/crossref_metadata_2025 huggingface dataset:
Conditional Knockout of Mouse Insulin‐Like Growth Factor‐1 Gene Using the Cre/loxP System
Authors: Liu Jun‐Li , Yakar Shoshana , LeRoith Derek
Published: August 2010

Abstract. Insulin‐like growth factor‐1 (IGF‐1) is an essential growth factor for normal intrauterine development and postnatal growth. Mice with a complete deficiency of IGF‐1 (IGF‐1–null mice), created by homologous recombination, were found to exhibit postnatal lethality, growth retardation, infertility, and profound defects in the development of major organ systems. Furthermore, IGF‐1–null mice were resistant to growth hormone (GH) treatment in peri‐pubertal somatic growth. Using the Cre/loxP‐induced conditional knockout system, we generated a mouse that lacks IGF‐1 specifically in the liver, the primary site of IGF‐1 production. Interestingly, although circulating and serum levels of IGF‐1 were decreased by ≈ 75% in these mice, they exhibited no defect in growth or development. When administered exogenously, GH stimulated IGF‐1 production in several extra‐hepatic tissues as well as body growth. The “Somatomedin hypothesis” originally proposed that circulating IGF‐1 acting in various tissues mediate the effects of GH. These striking in vivo results, obtained using homologous recombination technology, call for a major modification of the Somatomedin hypothesis. These gene targeting studies confirm that IGF‐1 is essential for GH‐stimulated postnatal body growth. However, liver‐derived (endocrine) IGF‐1 is not essential for normal postnatal growth, though it does exert a negative feedback on GH secretion. Instead, local production of IGF‐1, acting in a paracrine/autocrine fashion, appears to mediate GH‐induced somatic growth. This review will discuss the effects of tissue‐specific IGF‐1 gene deficiency created by the Cre/loxP system versus the conventional IGF‐1 knockout.
Anatomy and Blood Supply of the Lower Four Cranial and Cervical Nerves: Relevance to Surgical Neck Dissection
Authors: Brown Henry , Hidden Genvieve , Ledroux Michelle , Poitevan Luciano
Published: August 2010

Abstract. This study is a continuation of previous work searching for possible anatomic reasons to explain variable and usually unpredictable postoperative pain and dysfunction after the same nerve losses with similar neck dissection operations. The study consisted of dissections of 19 deceased unpreserved elderly subjects arterially injected with dyed latex. Of the 19 subjects, 14 had brain stem and cervical spinal cord dissections, and all had neck dissections. The findings suggested two possible anatomic reasons for the pain and dysfunction: (i) The intracranial anatomy of the lower four cranial nerves, the glossopharyngeal (IX), the vagus (X), the spinal accessory (XI), and the hypoglossal (XII), was just as variable as the previously reported peripheral spinal accessory nerve plexus; and (ii) Both the intracranial and neck dissections indicated that the blood supply to the lower four cranial and cervical nerves, particularly to the brachial plexus, could be impaired by atherosclerosis and/or neuroforaminal impingement or operative loss. This loss of blood supply theoretically could result in ischemia as another possible cause of postoperative pain and dysfunction. It is concluded that because of the potential importance of each nerve and vessel, often unknown at operation, it is very important to spare as many of them as possible to avoid subsequent painful impairment.
Leptin Receptor Transcripts Are Constitutively Expressed in Placenta and Adipose Tissue with Advancing Baboon Pregnancy
Authors: Green Amy E. , O'neil Jennifer S. , Swan Kenneth F. , Bohm Rudolf P. , Ratterree Marion S. , Henson Michael C.
Published: August 2010

Abstract. The baboon (Papio sp.) is an accepted nonhuman primate model for the study of the endocrinology of human pregnancy. To further characterize this model with regard to leptin function, messenger RNA transcripts for both long (Ob‐RL) and short (Ob‐RS) leptin receptor isoforms were identified in maternal tissues at various stages of gestation. Thus, placental villous, subcutaneous and omental adipose tissues were collected upon cesarean delivery at early (Days 60–62), mid (Days 98–102) and late (Days 159–164) pregnancy (term ≈ 184 days). Additionally, amniochorion, decidua, and corpus luteum were collected in late gestation. Expression of Ob‐RL and Ob‐RS transcripts was determined in relation to constitutively expressed glyceraldehyde‐3‐phosphate dehydrogenase via reverse transcriptase‐polymerase chain reaction, and transcripts were localized within specific placental cell types by in situ hybridization. Ob‐RL and Ob‐RS transcripts were present in amniochorion, decidua, and corpus luteum at term and appeared constitutively expressed throughout gestation in placenta and adipose tissues. Ob‐RS was expressed in greater (P < 0.02) abundance than Ob‐RL in all tissues. Within the placenta, receptor isoforms were localized predominantly to the syncytiotrophoblast. The expression of leptin receptor transcripts in maternal adipose tissues, as well as in the syncytiotrophoblast, amniochorion, decidua, and corpus luteum, suggests the potential for autocrine/paracrine roles for the polypeptide in the endocrinology of primate pregnancy. These are the first such observations in a nonhuman primate and support the use of the baboon as a model for the study of leptin in human pregnancy.
Association Between Elevated Prolactin Levels and Circulating Erythroid Precursors in Dialyzed Patients
Authors: Bellone Graziella , Rollino Cristiana , Borsa Simona , Ferrero Ivana , Martina Guido , Carbone Anna , Mareschi Katia , Quarello Francesco , Piccoli Giuseppe , Emanuelli Giorgio , Matera Lina
Published: August 2010

Abstract. The prolactin (PRL) receptor (R), a member of the cytokine hemopoietin receptor superfamily, has been shown to activate early differentiation steps along the erythroid pathway. In particular PRL, a product of bone marrow stroma, induces functional erythropoietin (EPO)‐R on CD34+ hemopoietic progenitors. In this study, expression of EPO‐R mRNA and responsiveness to EPO were assessed on enriched hemopoietic progenitor cells (HPC) from seven hyperprolactinemic and three normoprolactinemic patients and two normal subjects. Expression of EPO‐R mRNA by semiquantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) was found in HPC of four out of seven hyperprolactinemic patients but not in normoprolactinemic patients or normal donors. Development of EPO‐dependent Colony Forming Unit‐Erythroid (CFU‐E) colonies in semi‐solid medium was observed only in hyperprolactinemic patients (six out of seven). A much higher number of CFU‐E colonies was observed in the four patients with a positive EPO‐R message. We conclude from these data that abnormally high levels of PRL may increase the number of EPO‐responsive hemopoietic precursors in vivo as they do in vitro. Since hyperprolactinemia associates in these patients with depressed EPO production, it may be regarded as a compensatory mechanism for the reduced availability of the hemopoietic factor.
Evidence of Endogenous Mono‐ADP‐Ribosylation of Cardiac Proteins Via Anti‐ADP‐Ribosylarginine Immunoreactivity
Authors: Schwab Christopher J. , Colville Martha J. , Fullerton Aaron T. , McMahon Kathryn K.
Published: August 2010

Abstract. Arginine‐specific mono‐ADP‐ribosylation of proteins and arginine‐specific mono‐ADP‐ribosyltransferase occur in heart. We developed a polyclonal antiserum, R‐28, against ADP‐ribosylpolyarginine that recognized mono‐ADP‐ribosylated proteins and identified the major mono‐ADP‐ribosylation products of quail heart. Treatment of Immobilon‐bound ADP‐ribosylated Gs protein with hydroxylamine under conditions that remove ADP‐ribose from its arginines eliminated R‐28 immunoreactivity to Gs. Also, R‐28 immunoreactivity to quail heart proteins was removed by NaOH and phosphodiesterase I treatments. Similar treatment with mercuric chloride did not remove the immunoreactivity but did remove exogenously (via in vitro pertussis toxin treatment) added ADP‐ribose from cysteine of cardiac Gi/Go proteins. The antiserum did not appear to react with ADP‐ribosylasparagine of Rho (formed by C3 toxin), ADP‐ribosyldiphthamide of elongation factor 2 (formed by diphtheria toxin) in quail heart preparations, or polyADP‐ribosylated proteins of a neonate rat cardiac nuclear preparation. Thus, the R‐28 antiserum appears to contain predominantly antibodies directed against ADP‐ribosylarginine. To test the usefulness of R‐28, immunoblotting of subcellular fractions of quail heart was performed. R‐28 showed the greatest immunoreactivity in the sarcolemma with significant immunoreactivity in denser membrane fractions. The cytosol also contained an immunoreactive band distinct from those found in the membranes. Hydroxylamine treatment eliminated immunoreactivity in the sarcolemma and denser membrane fractions but not the cytosol, suggesting the membranous immunoreactive bands contain ADP‐ribosylarginine. In conclusion, a polyclonal antiserum that recognizes ADP‐ribosylarginine proteins has been raised. The usefulness of the antiserum is demonstrated by the characterization of endogenous arginine mono‐ADP‐ribosylation products in quail heart. The quail heart has several sarcolemmal and denser membrane fraction proteins that appear to be mono‐ADP‐ribosylated on arginines.
Aluminum Increases Levels of β‐Amyloid and Ubiquitin in Neuroblastoma But Not in Glioma Cells
Authors: Campbell A. , Kumar A. , La Rosa F. G. , Prasad K. N. , Bondy S. C.
Published: August 2010

Abstract. Several epidemiological studies suggest the involvement of aluminum (Al) in the pathogenesis of Alzheimer's disease (AD). There is an increase in the levels of Aβ and ubiquitin in the pathological lesions of AD. Therefore, we have investigated whether aluminum (Al) treatment alters the levels of Aβ and ubiquitin in murine neuroblastoma (NBP2) and rat glioma (C‐6) cell cultures. At a low concentration (10 μM), aluminum sulfate stimulated the level of immunoreactive Aβ and ubiquitin in NBP2 cells without changing the levels of the amyloid precursor protein (APP). However, at higher concentrations (100 and 500 μM), aluminum failed to elicit any significant effect on β‐amyloid, whereas ubiquitin levels continued to increase. No changes in the Aβ and ubiquitin content were found in the C‐6 glioma cells following treatment with Al at any of the concentrations tested. Exposure of cells to aluminum salts did not alter the rate of proliferation in either of the two cell lines. These data suggest that one of the mechanisms by which Al may play a role in AD is by promoting the formation of Aβ and ubiquitin in neurons.
Cardiac Opioids
Authors: Barron Barbara A.
Published: August 2010

Abstract. Opioid peptides have long been considered as neuropeptides or neurotransmitters. The more recent discovery of these same peptides in non‐neuronal tissue suggests that the peptides may have autocrine, paracrine, or endocrine functions as well. The opioid peptides, enkephalins, dynorphins, and endorphins, have been found in isolated cardiac myocytes and heart tissue. This review will cover the recent literature on opioid peptides in respect to cardiac distribution, biochemistry, and function.
Does the Insulin‐Like Growth Factor System Interact with Prostaglandins and Proinflammatory Cytokines During Neurodegeneration?
Authors: Lackey Brett R. , Gray Sandra L. , Henricks Donald M.
Published: August 2010

Abstract. Prostaglandins and proinflammatory cytokines are implicated in the etiology of neurodegenerative diseases, such as Alzheimer's disease. Signaling cascades initiated by these factors may result in reactive oxygen species generation and cell death. The insulin‐like growth factors (IGF) are ubiquitous polypeptides involved in all aspects of growth and development. Additionally, the IGF are regarded as survival factors that display potent antiapoptotic activity. Interfering with IGF production, distribution, or signaling may result in greater susceptibility to apoptotic stimuli. In neurodegenerative conditions, the IGF appear to be antagonized by prostaglandins and proinflammatory cytokines. In this review, the relationship among specific prostaglandins, the proinflammatory factors, tumor necrosis factor, interleukin‐1, and interleukin‐6, and the IGF system will be investigated.
Topical Insulin and Accumulation of Excitotoxic and Other Amino Acids in Ischemic Rat Cerebral Cortex
Authors: Guyot L. L. , Diaz F. G. , O'regan M. H. , Song D. , Phillis J. W.
Published: August 2010

Abstract. Insulin plays a neuroprotectant role in the brain and spinal cord during ischemia. However, studies have shown insulin to increase the sensitivity of cultured cortical cells to glutamate toxicity. The present study looked at the relationship between topically administered insulin (1 mIU insulin/ml and 100 mIU insulin/ml) during a four‐vessel model of global ischemia and the accumulation of amino acids, especially glutamate, from the ischemic rat cerebral cortex. The lower dose of insulin was found to attenuate the release of excitotoxic and other amino acids from the cortex in ischemia/reperfusion. This may occur because insulin increases glucose availability to glial cells resulting in maintenance of glycolysis and ionic pumps that can reduce glutamate release and maintain uptake during ischemia/reperfusion. The higher dose of insulin, which significantly increased the amount of aspartate, glutamate, taurine, and GABA during reperfusion, may act to stimulate the amount of glycogen stored in astrocytes, reducing the availability of glucose for metabolic purposes.
The Familial Mediterranean Fever Protein Interacts and Colocalizes with a Putative Golgi Transporter
Authors: Chen Xiaoguang , Bykhovskaya Yelena , Tidow Nicola , Hamon Melanie , Bercovitz Zoya , Spirina Olga , Fischel‐Ghodsian Nathan
Published: August 2010

Abstract. The biological function of pyrin, the protein mutated in Familial Mediterranean Fever (FMF), has not been elucidated. Based on sequence homology, a transcription factor activity was proposed for this neutrophil‐specific protein. In a yeast two‐hybrid assay, neither transcription activation activity nor any self interaction was detected for pyrin. Screening of an expression cDNA library of peripheral blood leukocytes using as bait the carboxyl portion of pyrin (amino acids 557–781), which contains most of the FMF mutations, led to the identification of P/M‐IP1 (pyrin/marenostrin interacting protein 1). A splice variant of P/M‐IP1, GTC‐90, had previously been described as a component of the 13S hetero‐oligomeric protein complex that stimulates in vitro Golgi transport. We have now shown that P/M‐IP1 colocalizes with pyrin in the perinuclear cytoplasm of Cos‐7 cells and that the interaction between these two proteins is impaired by FMF causing mutations in pyrin. These data suggest that, at some stage of its functional pathway, pyrin resides in the cytoplasm and might be involved in, or impacted by, cellular protein sorting by the Golgi apparatus. The data also imply that P/M‐IP1 may be involved in the abnormal inflammatory response that occurs in patients with FMF.
Prolactin Stimulation of Iodide Uptake and Incorporation into Protein Is Polyamine‐Dependent in Mouse Mammary Gland Explants
Authors: Rillema James A. , Collins Sarah , Williams Charles H.
Published: August 2010

Abstract. Previous studies have demonstrated that the prolactin stimulation of most lactational processes (casein, lactose, and triglyceride synthesis) requires an earlier stimulating effect of prolactin on the synthesis of the polyamines. Spermidine appears to be the specific polyamine required for prolactin to enhance milk product synthesis. Inorganic iodide is present in milk at more than an order of magnitude higher concentration than that of the maternal plasma. Since prolactin stimulates iodide accumulation in milk, the goal of these studies was to determine the role of the polyamines in this hormone response. Two drugs were employed in these studies: DFMO (difluoromethylornithine), which inhibits ornithine decarboxylase, and MGBG [methylglyoxal bis(guanyl‐hydrazone)], which inhibits S‐adenosyl methionine decarboxylase. In mammary gland explants from midpregnant (10–14 days of pregnancy) mice, MGBG at 100 μM abolished the prolactin stimulation of iodide uptake and incorporation into milk proteins, whereas DFMO caused a concentration‐dependent inhibition of the PRL response. Selected sensitivity of the MGBG and DFMO inhibitions was validated by a reversal of the drug inhibitions with the addition of 1 mM spermidine to the culture medium. These data suggest that the polyamine signaling pathway is involved in the prolactin stimulation of iodide uptake into milk.
State‐Dependent Expression of Pressure Diuresis in Conscious Rats
Authors: Steele Janet E. , Koch Lauren G. , Brand Paul H.
Published: August 2010

Abstract. In 1967, Guyton and Coleman modeled pressure diuresis as the underlying, essential, long‐term mechanism that regulates arterial pressure when sodium intake changes. Other mechanisms that influence renal function interact with pressure diuresis to achieve sodium balance and determine the blood pressure. Increases in sodium intake suppress sodium conserving mechanisms and activate natriuretic mechanisms; decreases in sodium intake have the opposite effect. If the Guyton‐Coleman model is correct, then pressure diuresis should be more readily detected in animals on a high‐salt diet than in animals on a low‐salt diet. We measured spontaneous changes in arterial pressure and urine flow in conscious rats fed low‐salt (0.4% NaCl) and high‐salt (8.0% NaCl) chow. For 10 rats fed a high‐salt diet, arterial pressure and urine flow were positively correlated in 19 of 32 (59%) trials. In 10 rats fed a low‐salt diet, a positive correlation was observed in 10 of 33 (30%) trials. Chi‐square analysis revealed that differences in Na+ content of the diet were significantly associated with the probability of a positive relationship between blood pressure and urine flow. These results support the hypothesis that the expression of pressure diuresis across time is dependent on the state of sodium balance.
Prevention of N‐Methylnitrosourea‐Induced Colon Carcinogenesis in Rats by Oxygenated Carotenoid Capsanthin and Capsanthin‐Rich Paprika Juice
Authors: Narisawa Tomio , Fukaura Yoko , Hasebe Makiko , Nomura Seiko , Oshima Shunji , Inakuma Takahiro
Published: August 2010

Abstract. Epidemiological and animal studies have provided evidence that dietary carotenoids may reduce the risk of certain types of cancer. An inhibitory activity of oxygenated carotenoid capsanthin, a potent antioxidant, and paprika juice rich in capsanthin (3.54 mg/100 ml) against colon carcinogenesis was investigated in F344 rats. In Experiment I (short‐term assay), six rats each were given a gavage of 5 mg, 0.2 mg, or 0.008 mg capsanthin six times a week for Weeks 2–6 after receiving three intrarectal doses of 4 mg N‐methylnitrosourea in Week 1. The number of colonic aberrant crypt foci, preneoplastic lesions, at Week 6 was significantly fewer (by 42%) in the 0.2 mg capsanthin group, but not in other groups, than the control group. In Experiment II (long‐term assay), five groups of 30 or 25 rats each received an intrarectal dose of 2 mg N‐methylnitrosourea three times a week for Weeks 1–3, and had either of 10 p.p.m. or 2 p.p.m. capsanthin solutions, 1:2.5 and 1:16.7 diluted solution of paprika juice (containing 10 p.p.m. or 2 p.p.m. capsanthin), and tap water (control fluid) as drinking fluid throughout the experiment. The experimental groups were fed 0.2 mg or 0.04 mg capsanthin/day/rat. The colon cancer incidence at Week 30 was significantly lower in the highly diluted paprika juice group (40%), but not in the moderately diluted paprika juice group (60%) and the capsanthin solution groups (68% and 68%) than the control group (83%). The results suggested that paprika juice may affect colon carcinogenesis. However, capsanthin alone failed to inhibit colon tumorigenesis, in spite of suppression of aberrant crypt foci formation in the short‐term assay. Further studies are needed to explain this discrepancy.
Differential Effects of Maturation on Nicotinic‐ and Muscarinic Receptor–Induced Ion Secretion in Guinea Pig Distal Colon
Authors: Powell Adrianne R. , Reddix Rhoda A.
Published: August 2010

Abstract.The incidence of constipation increases with age. This has been linked to age‐related changes in the structure and function of myenteric neurons regulating intestinal motility; however, the role of submucous neurons is unknown. The aim of this study was to determine the effect of maturation on cholinergic receptor–induced ion secretion in guinea pig colon. Changes in the short‐circuit current (Isc) and tissue conductance were monitored in muscle‐stripped colonic segments from young (3–4‐month‐old) and mature (12–15‐month‐old) male guinea pigs. Thirty‐one percent of colonic segments from young guinea pigs exhibited ongoing neural activity, which was absent in mature animals. Baseline Isc was significantly higher only in young guinea pig tissues with ongoing activity. Tissue conductance was similar in all tissues. Electrical field stimulation caused a biphasic increase in the Isc. At 15 V/10 Hz, only Peak 1 was attenuated, whereas both peaks were reduced in mature guinea pigs at 10 V/5Hz. 1,1,dimethyl‐4‐phenyl‐piperazinium(DMPP)–induced ion secretion was blunted in mature guinea pigs. Atropine reduced the 1,1,dimethyl‐4‐phenyl‐piperazinium response only in young guinea pigs. Carbachol‐induced ion secretion was similar in tissues from both age groups. In conclusion, nicotinic receptor–induced secretion mediated by both cholinergic and noncholinergic secretomotor neurons was blunted; however, epithelial muscarinic receptor activity was unaltered during maturation.
The Possible Role of Prolactin in the Circadian Rhythm of Leptin Secretion in Male Rats
Authors: Mastronardi C. A. , Walczewska A. , Yu W. H. , Karanth S. , Parlow A. F. , McCann S. M.
Published: August 2010

Abstract. In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the early morning and a maximum in the middle of the night. By taking blood samples from adult male rats every 3 hr for 24 hr, we determined that a circadian rhythm of plasma leptin concentrations also occurs in the rat with a peak at 0130h and a minimum at 0730h. To determine if this rhythm is controlled by nocturnally released hormones, we evaluated the effect of hormones known to be released at night in humans, some of which are also known to be released at night in rats. In humans, prolactin (PRL), growth hormone (GH), and melatonin are known to be released at night, and adrenocorticotropic hormone (ACTH) release is inhibited. In these experiments, conscious rats were injected intravenously with 0.5 ml diluent or the substance to be evaluated just after removal of the first blood sample (0.3 ml), and additional blood samples (0.3 ml) were drawn every 10 min thereafter for 2 hr. The injection of highly purified sheep PRL (500 μg) produced a rapid increase in plasma leptin that persisted for the duration of the experiment. Lower doses were ineffective. To determine the effect of blockade of PRL secretion on leptin secretion, α bromoergocryptine (1.5 mg), a dopamine‐2‐receptor agonist that rapidly inhibits PRL release, was injected. It produced a rapid decline in plasma leptin within 10 min, and the decline persisted for 120 min. The minimal effective dose of GH to lower plasma leptin was 1 mg/rat. Insulin‐like growth factor (IGF‐1) (10 μg), but not IGF‐2 (10 μg), also significantly decreased plasma leptin. Melatonin, known to be nocturnally released in humans and rats, was injected at a dose of 1 mg/rat during daytime (1100h) or nighttime (2300h). It did not alter leptin release significantly. Dexamethasone (DEX), a potent glucocorticoid, was ineffective at a 0.1‐mg dose but produced a delayed, significant increase in leptin, manifest 100–120 min after injection of a 1 mg dose. Since glucocorticoids decrease at night in humans at the time of the maximum plasma concentrations of leptin, we hypothesize that this increase in leptin from a relatively high dose of DEX would mimic the response to the release of corticosterone following stress in the rat and that glucocorticoids are not responsible for the circadian rhythm of leptin concentration. Therefore, we conclude that an increase in PRL secretion during the night may be responsible, at least in part, for the nocturnal elevation of leptin concentrations observed in rats and humans.
Tissue‐Specific Expression of the Uncoupling Protein Family in Streptozotocin‐Induced Diabetic Rats
Authors: Hidaka Shuji , Yoshimatsu Hironobu , Kakuma Tetsuya , Sakino Hiroshi , Kondou Seiya , Hanada Reiko , Oka Kyoko , Teshima Yasushi , Kurokawa Mamoru , Sakata Toshiie
Published: August 2010

Abstract. The vulnerability of streptozotocin (STZ)‐induced diabetic rats to cold stress has been established. One of the elements controlling body temperature is thermogenesis, in which uncoupling protein (UCP) is known to play an important role. We have examined UCP2 and UCP3 expressions in brown adipose tissue (BAT), white adipose tissue (WAT), and skeletal muscle (MSL) during the acute and chronic phases of STZ‐induced diabetes in rats. The long‐term effect and the effect of insulin treatment thereafter were also unexplored previously and are examined in this study. In the acute phase of diabetes (2.5 days after STZ injection), UCP2 gene expression in BAT, WAT, and MSL, and UCP3 expression in the muscle were significantly increased. In the chronic phase of diabetes (21 days after STZ injection), UCP2 and UCP3 expression in the MSL were restored to the control levels without insulin supplementation. UCP2 in BAT and WAT remained high in the chronic phase, whereas UCP3 expression in BAT and WAT, which did not change in the acute phase, was significantly decreased. Insulin supplementation restored UCP2 expression in BAT and WAT, but over‐corrected UCP3 in WAT above the control and did not affect UCP3 expression in BAT. Insulin supplementation depressed UCP3 expression in the MSL below control. These results indicate that the effects of STZ‐induced diabetes on UCPs gene expression are tissue‐specific as well as dependent on the duration of diabetes.
Albumin Facilitates Zinc Acquisition by Endothelial Cells
Authors: Rowe David J. , Bobilya Dennis J.
Published: August 2010

Abstract. Albumin has long been observed to have a marked influence on the delivery of zinc to cells, but the mechanism of the interaction remains elusive. We examined whether albumin facilitates the acquisition of zinc by endothelial cells. Cultures of endothelial cells were used to analyze binding and acquisition of zinc and albumin to test this interaction. Our results indicate that albumin plays a role in facilitating the physiological delivery of zinc to endothelial cells. Albumin receptors that preferentially recognize albumin molecules carrying a zinc atom were demonstrated on the endothelial cell surface. Endocytosis is instrumental in albumin uptake, which was also consistently true of zinc uptake. Zinc and albumin were acquired by the cells in a 1:1 molar stoichiometry during the first 20 min of incubation in a medium with equimolar concentrations of zinc and albumin. The amount of albumin associated with the cells stabilized after 30 min, whereas the amount of zinc continued to increase. One possible explanation for this result is that a physiological route for zinc delivery into endothelial cells is by co‐transport with albumin via receptor‐mediated endocytosis.
Scientific Misconduct and Research Integrity for the Bench Scientist
Authors: Pascal Chris B.
Published: August 2010

Abstract. This paper describes the role of the Office of Research Integrity (ORI), a component of the Public Health Service (PHS), in defining scientific misconduct in research supported with PHS funds and in establishing standards for responding to allegations of misconduct. The principal methods by which ORI exercises its responsibilities in this area are defining what types of behaviors undertaken by research investigators constitute misconduct, overseeing institutional efforts to investigate and report misconduct, and recommending to the Assistant Secretary for Health (ASH) PHS administrative actions when misconduct is identified. ORI also takes affirmative steps to promote research integrity through education, training, and other initiatives. The role of the research institution in responding to misconduct and promoting research integrity is complementary and overlapping with ORI's efforts but, as the employer of research investigators and front‐line manager of the research, the institution has a greater opportunity to promote the highest standards of integrity in the day‐to‐day conduct of research. Finally, legal precedent established through civil litigation has played an important role in defining the standards that apply in determining when a breach of research integrity has occurred.
The Effect of Hyaluronan on Elastic Fiber Injury In Vitro and Elastase‐Induced Airspace Enlargement In Vivo
Authors: Cantor Jerome O. , Shteyngart Bronislava , Cerreta Joseph M. , Liu Ming , Armand Gerard , Turino Gerard M.
Published: August 2010

Abstract. This laboratory has previously described a method of preventing air‐space enlargement in experimental pulmonary emphysema using aerosolized hyaluronan (HA). Although it was found that HA preferentially binds to elastic fibers (which undergo breakdown by elastases in emphysema), it remains to be shown that such attachment actually prevents damage to the fibers. In the current study, cell‐free radiolabeled extracellular matrices, derived from rat pleural mesothelial cells, were used to test the ability of low molecular weight (≈ 100 kDa) streptococcal HA to prevent elastolysis. Coating the matrices with HA significantly decreased elastolysis (P<0.05) induced by porcine pancreatic elastase (43%), human neutrophil elastase (53%), and human macrophage metalloelastase (80%). Concomitant in vivo studies examined the ability of an aerosol preparation of the streptococcal HA to prevent experimental emphysema induced by intratracheal administration of porcine pancreatic elastase. As seen with earlier studies involving bovine tracheal HA, a single aerosol exposure significantly decreased elastase‐induced airspace enlargement, as measured by the mean linear intercept (107.5 vs 89.6 μm; P < 0.05). Furthermore, repeated exposure to the HA aerosol for 1 month did not reveal any morphological changes in the lung. The results provide further evidence that aerosolized HA may be an effective means of preventing pulmonary emphysema and perhaps other lung diseases that involve elastic fiber injury.
Proliferation of Peripheral Blood Mononuclear Cells Increases Riboflavin Influx
Authors: Zempleni Janos , Mock Donald M.
Published: August 2010

Abstract. Previously we demonstrated that proliferation of peripheral blood mononuclear cells (PBMC) causes a five‐fold increase in cellular uptake of biotin; this increase is mediated by an increased number of biotin transporters on the PBMC surface. In the present study, we investigated the specificity of this phenomenon by determining whether the cellular uptake of riboflavin also increases in proliferating PBMC and whether the increase is also mediated by an increased number of transporters per cell. We characterized [3H]riboflavin uptake in both quiescent and proliferating PBMC. In quiescent PBMC, [3H]riboflavin uptake exhibited saturation kinetics and was reduced by addition of unlabeled riboflavin (P < 0.05) or lumichrome (P < 0.01). These observations are consistent with transporter‐mediated uptake. [3H]Riboflavin uptake was reduced at 4°C compared with 37°C (P < 0.01) and by 2,4‐dinitrophenol (P < 0.05) but not by ouabain or incubation in sodium‐free medium. These data provide evidence for an energy‐dependent but sodium‐independent transporter. Proliferating PBMC accumulated approximately four times more [3H]riboflavin than quiescent PBMC (P < 0.05). Because both transporter affinity and transporter number per cell (as judged by maximal transport rate) were similar in quiescent and proliferating PBMC, we hypothesize that the increased riboflavin uptake by proliferating PBMC reflects only increased cellular volume. To test this hypothesis, PBMC volume was reduced using hyperosmolar medium; [3H]riboflavin uptake decreased to about 50% of isotonic controls (P < 0.01). Thus we conclude that proliferating PBMC increase cellular content of riboflavin and biotin by two different mechanisms.
Urinary Excretion of LH and Testosterone from Male Rats During Exposure to Increased Gravity: Post‐Spaceflight and Centrifugation
Authors: Ortiz Rudy M. , Wade Charles E. , Morey‐Holton Emily
Published: August 2010

Abstract. A dissociation between plasma luteinizing hormone (LH) and testosterone (T) appears to exist during exposure to altered gravity. The pulsatile nature of LH release and the diurnal variability of T secretion may mask or bias the effects of altered gravity on the pituitary‐gonadal axis when analyzing plasma concentrations. Therefore, we examined the relationship between the excretion of urinary LH and T in male Sprague‐Dawley rats during exposure to increased gravity upon return to Earth following a 14‐day spaceflight (n = 6) and by 12 days of centrifugation at 2g (n = 8). Excreted LH and T were elevated on the first 3 days postflight. Excreted T was elevated between Days 1 and 8 of centrifugation; however, excreted LH was reduced on Days 2 and 3 compared with control animals. Excreted LH and T were significantly correlated (R = 0.731 and 0.706, respectively) in postspaceflight and centrifuged animals. Correlation curves had similar slopes (0.0213 and 0.023, respectively), but different y‐intercepts (–1.43 and 3.32, respectively). The sustained increase in excreted T during centrifugation suggests that the pituitary‐gonadal axis in postspaceflight animals may adapt quicker to increased gravity. The upward shift in the correlation curve exhibited by the centrifuged animals suggests that the sensitivity of LH‐induced T release is increased in these animals. The previous dissociation between plasma LH and T during altered gravity was not observed in the present study in which excreted LH and T were measured.
Role of Nitric Oxide and Superoxide in Acute Cardiac Allograft Rejection in Rats
Authors: Akizuki Eiji , Akaike Takaaki , Okamoto Sinichirou , Fujii Shigemoto , Yamaguchi Yasuo , Ogawa Michio , Maeda Hiroshi
Published: August 2010

Abstract.The role of NO and superoxide (O2−) in tissue injury during cardiac allograft rejection was investigated by using a ratex vivoorgan perfusion system. Excessive NO production and inducible NO synthase (iNOS) expression were observed in cardiac allografts at 5 days after cardiac transplantation, but not in cardiac isografts, as identified by electron spin resonance spectroscopy and Northern blotting. Cardiac isografts or allografts obtained on Day 5 after transplantation were perfused with Krebs bicarbonate buffer with or without various antidotes for NO or O2−, includingNω‐monomethyl‐L‐arginine (L‐NMMA; 1 mM), 2‐phenyl‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide (PTIO; 100 μM), 4‐amino‐6‐hydroxypyrazolo[3,4‐d]pyrimidine (AHPP; a xanthine oxidase inhibitor; 100 μM), and superoxide dismutase (SOD; 100 units/ml). Treatment of the cardiac allografts with PTIO showed most remarkable improvement of the cardiac injury as revealed by significant reduction in aspartate transaminase, lactate dehydrogenase, and creatine phosphokinase concentrations in the perfusate. Similar but less potent protective effect on the allograft injury was observed by treatment with L‐NMMA, AHPP, and SOD. Immunohistochemical analyses for iNOS and nitrotyrosine indicated that iNOS is mainly expressed by macrophages infiltrating the allograft tissues, and nitrotyrosine formation was demonstrated not only in macrophages but also in cardiac myocytes of the allografts, providing indirect evidence for the generation of peroxynitrite during allograft rejection. Our results suggest that tissue injury in rat cardiac allografts during acute rejection is mediated by both NO and O2−, possibly through peroxynitrite formation.
Ants as Indicators of Restoration Success at a Uranium Mine in Tropical Australia
Authors: Andersen Alan N.
Published: August 2010

The composition and structure of ant communities were used to assess the success of the preliminary restoration program at Ranger uranium mine in the seasonal tropics of northern Australia. Ants were surveyed at eight sites, including two relatively undisturbed control sits, within the Ranger lease. The revegetated sites represented a range of variables likely to influence restoration success: revegetation age (two, four, and eight years), proximity to undisturbed sites (which act as potential sources of recolonization), and burning treatment. Revegetation at most sites was dominated by fast‐growing species ofAcacia.There was a clear succession of ant species across revegetated sites. Initial colonization was by species ofIridomyrmex, but as plant cover and litter development increased these were replaced by broadly adapted, opportunist species, especially the introducedParatrechina longicornis. Ant recolonization was very slow at isolated sites, with only 12 species present after eight years (the oldest site available). This compares with 21 species after only four years at a site located close to potential sources of recolonization. The ant community at this site, however, was very similar to that at another site located close to colonization sources, but eight years old. Ant succession therefore appeared to have stalled at this point, with species richness and composition bearing little resemblance to that at control sites. The heavy shade and litter produced by acacias were considered to be the major impediment to further change. Results from a site that had undergone a prescribed burn after two years, thereby breaking dominance by acacias and allowing for the establishment of a wide variety of plant taxa, suggest that such management practices may promote further colonization by ant species.
Microbial and Phosphate Dynamics in a Restored Shrub Steppe in Southwestern Wyoming
Authors: Allen Michael F.
Published: August 2010

Soil microbial activity and soil nutrients were monitored on a revegetated coal surface mine in southwestern Wyoming from the initial planting in 1982 through 1987. Total soil nitrogen (N) and organic matter did not change during this period. However, despite no changes in available phosphorus (P) concentrations, the total P declined over 50% during the five‐year period, with no apparent reduction in the loss rates. The greatest loss was in the bound inorganic P pool. Moisture appeared not to limit microbial mass‐C. Microbial mass‐C was higher under shrubs than in interspaces and increased with time. Total organic matter did not increase. Thus, the ratio of microbial mass‐C to organic matter‐C increased during the study period. This suggests that the input of readily decomposable substrate may limit microbial activity. During the study period, all above‐ground litter was removed by wind. Root production in the surface soils was low and highly variable and, in this habitat, probably did not contribute largely to the organic matter status. These data suggest that despite an apparent recovery of many parameters used to indicate reclamation or restoration success, the soil‐bound P pools could be undergoing a loss. Microbial‐C and organic matter changes indicate a system that is not approaching equilibrium within the required monitoring period of most restoration efforts. These parameters could eventually reduce the recovery potential of restored sites.
Riparian Restoration in the Western United States: Oveview and Perspecive
Authors: Goodwin Craig N. , Hawkins Charles P. , Kershner Jeffrey L.
Published: August 2010

This historical and conceptual overview of riparian ecosystem restoration discusses how riparian ecosystems have been defined, describes the hydrologic, geomorphic, and biotic processes that create and maintain riparian ecosystems of the western USA, identifies the main types of anthropogenic desturbances occurring in these ecosystems, and provides an overview of restoration methods for each disturbance type. We suggest that riparian ecosystems consist of two zones: Zone I occupies the active floodplain and is frequently inundated and Zone II extends from the active floodplain to the valley wall. Successful restoration depends n understanding the physical and biological processes that influence natural riparian ecosystems and the types of disturbance that have degraded riparian areas. Thus we recommend adopting a process‐based approach for riparian restoration. Disturbances to riparian ecosystems in the western USA result from streamflow modifications by dams, reservoirs, and diversions; stream channelization; direct modification of the riparian ecosystem; and watershed disturbances. Four topics should be addressed to advance the state of science for restoration of riparian ecosys‐tems: (1) interdisciplinary approaches, (2) a unified framework, (3) a better understanding of fundamental riparian ecosystem processes, and (4) restoration po‐tential more closely related to disturbance type. Three issues should be considered regarding the cause of the degraded environment: (1) the location of the causative disturbance with respect to the degraded riparian area, (2) whether the disturbance is ongoing or can be elim‐inated, and (3) whether or not recovery will occur nat‐urally if the disturbance is removed.
Setting Riparian/Aquatic Restoration Objectives Within a Watershed Context
Authors: Kershner Jeffrey L.
Published: August 2010

Declines in native plant and animal communities have prompted new interest in the restoration of aquatic and riparian ecosystems. Past restoration activities typically have been site specific, with little thought to processes operating at larger scales. A watershed analysis process developed in the Pacific northwest identifies four operating scales useful in developing restoration priorities: region, basin, water‐shed, and specific site. Wtershed analysis provides a template for restoration practitioners to use in prioritizing restoration activities. The template identifies seven key steps necessary to understand and develop restoration priorities: (1) characterization, (2) identification of key issues and questions, (3) documentation of current conditions, (4) description of reference conditions, (5) identification of objectives, (6) summary of conditions and determination of causes, and (7) recommendations. When a similar process was used in the Uinta Mountains, Utah, and in the Sluslaw National Forest, Orgon, specialists were able to identify key habitat conditions and habitat forming processes and then to establish restoration priorities and implement the appropriate activities. Watershed analysis provides a valuable set of tools for identifying restoration activities and is currently being used throughout the Pacific Northwest to develop management strategies and restoration priorities. Although the analysis requires significant time, money, and personnel, experience suggests that watershed analysis provides valuable direction for managing aquatic and riparian resources.
A Comparison of Approaches to Prioritizing Sites for Riparian Restoration
Authors: Kentula Mary E.
Published: August 2010

This study compares the results of Olson and Harris (1997) and Russell et al. (1997) in their work to prioritize sites for riparian restoration in the San Luis Rey River watershed. Olson and Harris defined reaches of the mainstem and evaluated the relative potential for restoration and protection based on cover of natural vegetation, land use, and connectivity. Then they used data on geomorphic conditions, plant species composition, and community structure to prescribe strategies for restoration. Russell et al. used a modeling approach within a geographic information system to combine data on wetness and land use/land cover to identify areas with potential for protection and restoration. They prioritized the areas based on patch size and proximity to extant riparian habitat. The main‐stem and associated floodplain defined by Olson and Harris was more than twice the size of the area defined by Russell et al., because Olson and Harris considered the entire valley floor, whereas Russell et al. used a wetness index to identify saturated zones within the floodplain. For seven of the twelve management units delineated along the mainstem, the two studies agreed on a strategy of restoration or protection. They differed on two. No comparison could be made of the three units for which Olson and Harris used project review, a unique category. Agreement of the results is due to the similarity of criteria used to identify and rank sites for protection and restoration; disagreement is due primarily to the level of resolution of the data. Both approaches have potential for use in watershed‐level planning. The predictive power of the two approaches may be maximized when they are used in a complementary fashion.
Hydrology and Bauxite Mining on the Darling Plateau
Authors: Croton James T. , Reed Amanda J.
Published: August 2010

A review was undertaken of the interaction between bauxite mining, its restoration, and the hydrology of the Darling Plateau. Alcoa’s mining operation is predominately within the water supply catchments of Perth, giving rise to three hydrological issues: turbidity, stream yields, and stream salinity. Turbidity management is effected through attention to detail in day‐to‐day operations. Due to the high rates of evapotranspiration, yields from Jarrah forest catchments are low by normal standards, varying from 25% of rainfall in the highest rainfall area to less than 1% of rainfall in the lowest; this has been further exacerbated by the below‐average rainfall since 1975. These low yields have resulted in increased interest in stream yields from mined and restored mine areas and how these may be maintained compared with unmined forest. Under current rainfall regimes, it is unlikely that there will be a significant salinity response due to Alcoa’s mining, but it is inadvisable to discount the salinity issue in the lower rainfall zone, and research will need to consider the possibility of further climate change.
Comment expliquer le déclin de Montréal comme centre de transports aériens: une question de géographie économique?
Authors: DISCAZEAUX CARINE , POLÈSE MARIO
Published: August 2010

L'objectif de cet article est de comprendre l'évolution des activités aériennes à Montréal. Plaque tournante majeure dans les années 1960, Montréal voit ses activités aériennes ralentir dès le milieu des années 1970. Quelles sont les origines véritables de ce ralentissement? Ce déclin est souvent attribuéà la construction d'un second aéroport international à Montréal‐Mirabel en 1975. Mais qu'en est‐il exactement? Ceci nous amène à nous interroger sur les facteurs de localisation des activités aériennes de manière générale. S'agit‐il d'une activité de service qui se localise selon une logique de places centrales, en fonction de la taille des villes? Faut‐il plutôt chercher ailleurs, par exemple dans les conditions technologiques et réglementaires propres à l'industrie? Pour y répondre, nous proposons une analyse en deux temps. D'abord, nous nous servirons des outils de régression afin d'évaluer l'importance du poids de l'économie locale comme facteur explicatif du trafic aérien. Cette première partie est essentiellement statique. Dans un deuxième temps, nous effectuerons une analyse à caractère davantage historique des activités aériennes de Montréal depuis 1945, pour renouer à la fin avec les résultats de l'analyse de régression.