bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin preserves fetal growth in rats by protecting against ischemia/reperfusion‐induced oxidative/nitrosative mitochondrial damage in the placenta
Authors: Nagai Ryuhei , Watanabe Kazushi , Wakatsuki Akihiko , Hamada Fumiaki , Shinohara Koichi , Hayashi Yoshihiro , Imamura Rina , Fukaya Takao
Published: March 2008

Abstract:  We have previously demonstrated that melatonin protects against ischemia/reperfusion‐induced oxidative damage to mitochondria in the fetal rat brain. The purpose of the present study was to evaluate the effects of maternally administered melatonin on ischemia/reperfusion‐induced oxidative placental damage and fetal growth restriction in rats. The utero‐ovarian arteries were occluded bilaterally for 30 min in rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. Melatonin solution (20 μg/mL) or the vehicle alone was administered orally during pregnancy. A sham operation was performed in control rats, which were treated with vehicle alone. Laparotomy was performed on day 20 of pregnancy and the number and weight of fetal rats and placentas were measured. Placental mitochondrial respiratory control index (RCI), a marker of mitochondrial respiratory activity, was also calculated for each group. Using immunohistochemistry, we investigated the degree of immunostaining of 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG), a marker of oxidative DNA damage, and redox factor‐1(ref‐1), which repairs DNA damage and acts as a redox‐modifying factor in rat placenta. Predictably, the ischemia/reperfusion operation significantly decreased the weight of fetal rats and placentas and the RCI. Melatonin prevented ischemia/reperfusion‐induced changes in RCI (1.55 ± 0.05 to 1.83 ± 0.09, P < 0.05) and fetal growth (3.04 ± 0.17 to 3.90 ± 0.1, P < 0.0001). Immunohistochemistry revealed significant positive staining for 8‐OHdG and ref‐1 following ischemia/reperfusion; these effects were also reduced by melatonin treatment. Results indicated that ischemia/reperfusion‐induced oxidative placental DNA and mitochondrial damage and fetal growth restriction can be prevented by maternally administered melatonin.
Epigenetic targets for melatonin: induction of histone H3 hyperacetylation and gene expression in C17.2 neural stem cells
Authors: Sharma Rohita , Ottenhof Thomas , Rzeczkowska Paulina A. , Niles Lennard P.
Published: March 2008

Abstract:  We have reported the induction of glial cell line‐derived neurotrophic factor, a potent survival factor for dopaminergic neurons, in the C17.2 neural stem cell line following in vitro treatment with melatonin. Furthermore, we have detected the melatonin MT1 receptor in these cells. Given these findings and recent evidence that melatonin may play a role in cellular differentiation, we examined whether this indoleamine induces morphological and transcriptional changes suggestive of a neuronal phenotype in C17.2 cells. Moreover, in order to extend preliminary evidence of a potential role for melatonin in epigenetic modulation, its effects on the mRNA expression of several histone deacetylase (HDAC) isoforms and on histone acetylation were examined. Physiological concentrations of melatonin (nanomolar range) increased neurite‐like extensions and induced mRNA expression of the neural stem cell marker, nestin, the early neuronal marker β‐III‐tubulin and the orphan nuclear receptor nurr1 in C17.2 cells. The indoleamine also significantly increased mRNA expression for various HDAC isoforms, including HDAC3, HDAC5, and HDAC7. Importantly, treatment with melatonin for 24 hr caused a significant increase in histone H3 acetylation, which is associated with chromatin remodeling and gene transcription. Since the melatonin MT2 receptor was not detected in C17.2 cells, it is likely that the MT1 receptor is involved in mediating these physiological effects of melatonin. These findings suggest novel roles for melatonin in stem cell differentiation and epigenetic modulation of gene transcription.
The Social Function of the Law Faculty: Demographics, Republican Reform, and Professional Training at the Paris Law Faculty, 1870–1914
Authors: Savage John
Published: March 2008

In a high-profile newspaper editorial written in the fall of 1868, the future French premier Jules Ferry denounced the “lamentable” state of training in France's law faculties in no uncertain terms: “One must say that the lowly consideration that is given today in our courts to what was once legal science; the mania for judging and pleading only on the facts; the growing elasticity of texts and the lazy indiscipline of interpretation; the substitution of equity, that is to say arbitrariness, for the rule of law, have all created harmful trends that threaten all the good habits, the noble scruples, and all of the perhaps strict but salutary traditions of past times.” Given the limits placed on the press, suffrage, and the practice of law itself under the regime of Napoleon III, it is striking that Ferry would focus on France's law faculties as a primary area of concern. But like other critics who spoke out on the issue, Ferry saw the weakness of legal education as a symbol of the corruption of elites in Second Empire France, and education reform would be a hallmark of his tenure as Premier in republican governments of the 1880s. In addition to the momentous laws that bore his name making secondary education “obligatory, secular and free,” the reform of training for the professions was a priority for Ferry and others who followed his strain of moderate, or “opportunist,” republicanism.
The Psychological and Physical Health Effects of Stigma: The Role of Self‐threats
Authors: Eccleston Collette P.
Published: March 2008

Being a member of a group that is stigmatized (i.e., low status, devalued, negatively stereotyped, and victimized by prejudice and discrimination) can affect health. In this paper, I consider threats to the social self as a mediator in the relationship between stigmatizing experiences and health. I discuss experiences associated with stigmatization that can pose a potential threat to the sense of self and how each of these aspects of stigma relates to health. Our current knowledge is heavily centered on how discrimination experiences relate to health. More research is needed on how other aspects of stigma affect health. In addition, research addressing coping strategies, and especially how they influence health behaviors, will be useful in gaining a better understanding of the mechanisms through which stigma affects health.
Loss of life due to floods
Authors: Jonkman S.N. , Vrijling J.K.
Published: March 2008

This article gives an overview of the research on loss of life due to floods. The limited information regarding this topic is presented and evaluated. Analysis of global data for different flood types shows that the magnitude of mortality is related to the severity of the flood effects and the possibilities for warning and evacuation. Information from historical flood events gives a more detailed insight into the factors that determine mortality for an event, such as flood characteristics and the effectiveness of warning and evacuation. At the individual level, the occurrence of fatalities will be influenced by behaviour and individual vulnerability factors. Existing methods for the estimation of loss of life that have been developed for different types of floods in different regions are briefly discussed. A new method is presented for the estimation of loss of life due to floods of low‐lying areas protected by flood defences. It can be used to analyse the consequences and risks of flooding and thereby provide a basis for risk evaluation and decision‐making. The results of this research can contribute to the development of strategies to prevent and mitigate the loss of life due to floods.
Notes on TYachoma, Tüberolabium and Parapteroceras (Orchidaceae)
Authors: Wood Jeffrey J.
Published: March 2008

The genus Trachoma is considered congeneric with Tüberolabium. All necessary transfers to Tüberolabium are made. Four new combinations are made in the recently established Parapteroceras. A key to the species of Parapteroceras and a key to Parapteroceras and allied genera are provided.
Validations and new combinations in Cortinarius, with special emphasis on infrageneric taxa of subgenus Phlegmacium (Agaricales)
Authors: Brandrud Tor Erik , Melot Jacques
Published: March 2008

Part of the “Cortinarius, Flora Photographica, vol. I” in which six new combinations and thirty infrageneric names published for taxa in the genus Cortinarius are validated, including 7 sections and 21 subsections in the subgenus Phlegmacium.
Doped Nanocrystals
Authors: Norris David J. , Efros Alexander L. , Erwin Steven C.
Published: March 2008

The critical role that dopants play in semiconductor devices has stimulated research on the properties and the potential applications of semiconductor nanocrystals, or colloidal quantum dots, doped with intentional impurities. We review advances in the chemical synthesis of doped nanocrystals, in the theoretical understanding of the fundamental mechanisms that control doping, and in the creation of highly conducting nanocrystalline films. Because impurities can be used to alter the properties of nanoscale materials in desirable and controllable ways, doped nanocrystals can address key problems in applications from solar cells to bioimaging.
Another Approach to Consilience
Authors: Labinger Jay
Published: March 2008

Proust Was a Neuroscientist
.
By Jonah Lehrer
. Houghton Mifflin, Boston, 2007. 256 pp. $24, C$32.95. ISBN 9780618620104.

Artscience
. Creativity in the Post-Google Generation.
By David Edwards
. Harvard University Press, Cambridge, MA, 2008. 203 pp., $19.95, £12.95, €15. ISBN 9780674026254.

Many who dream of unifying scientific and humanistic thinking seem to hold a one-sided view of the resulting whole: that the study of topics in the arts and humanities should be informed by science. Lehrer and Edwards offer a range of examples that suggest the benefits from working in the other direction.
Use of Baculovirus-Expressed Glycoprotein H in an Enzyme-Linked Immunosorbent Assay Developed To Assess Exposure to Chelonid Fibropapillomatosis-Associated Herpesvirus and Its Relationship to the Prevalence of Fibropapillomatosis in Sea Turtles
Authors: Herbst Lawrence H. , Lemaire Shefali , Ene Ada R. , Heslin David J. , Ehrhart Llewellyn M. , Bagley Dean A. , Klein Paul A. , Lenz Jack
Published: March 2008

Chelonid fibropapillomatosis-associated herpesvirus (CFPHV) is an alphaherpesvirus believed to cause marine turtle fibropapillomatosis (FP). A serodiagnostic assay was developed for monitoring sea turtle populations for CFPHV exposure. CFPHV glycoprotein H (gH) expressed in recombinant baculovirus was used in an enzyme-linked immunosorbent assay (ELISA) to detect virus-specific 7S turtle antibodies. Using captive-reared green turtles (
Chelonia mydas
) with no history of virus exposure as “known negatives” and others with experimentally induced FP as “known positives,” the assay had 100% specificity but low sensitivity, as seroconversion was detected in only half of the turtles bearing experimentally induced tumors. Antibodies were detected only in samples collected after cutaneous fibropapillomas appeared, consistent with observations that tumors are significant sites of virion production and antigen expression and the possibility that prolonged/repeated virus shedding may be required for adequate stimulation of 7S antibody responses to gH. Natural routes of infection, however, may produce higher seroconversion rates. High gH antibody seroprevalences (∼80%) were found among wild green turtles in three Florida localities with different FP prevalences, including one site with no history of FP. In addition, all eight loggerhead turtles (
Caretta caretta
) tested were seropositive despite FP being uncommon in this species. The possibility that CFPHV infection may be common relative to disease suggests roles for environmental and host factors as modulators of disease expression. Alternatively, the possibility of other antigenically similar herpesviruses present in wild populations cannot be excluded, although antibody cross-reactivity with the lung/eye/trachea disease-associated herpesvirus was ruled out in this study.
PCR Method To Identify
Salmonella enterica
Serovars Typhi, Paratyphi A, and Paratyphi B among
Salmonella
Isolates from the Blood of Patients with Clinical Enteric Fever
Authors: Levy Haim , Diallo Souleymane , Tennant Sharon M. , Livio Sofie , Sow Samba O. , Tapia Milagritos , Fields Patricia I. , Mikoleit Matthew , Tamboura Boubou , Kotloff Karen L. , Lagos Rosanna , Nataro James P. , Galen James E. , Levine Myron M.
Published: March 2008

PCR methodology was developed to identify
Salmonella enterica
serovars Typhi, Paratyphi A, and Paratyphi B. One multiplex PCR identifies serogroup D, A, and B and Vi-positive strains; another confirms flagellar antigen “d,” “a,” or “b.” Blinded testing of 664 Malian and Chilean
Salmonella
blood isolates demonstrated 100% sensitivity and specificity.
High Temperature (30°C) Blocks Aerosol but Not Contact Transmission of Influenza Virus
Authors: Lowen Anice C. , Steel John , Mubareka Samira , Palese Peter
Published: March 2008

Influenza causes significant morbidity in tropical regions; however, unlike in temperate zones, influenza in the tropics is not strongly associated with a given season. We have recently shown that influenza virus transmission in the guinea pig model is most efficient under cold, dry conditions, which are rare in the tropics. Herein, we report the lack of aerosol transmission at 30°C and at all humidities tested. Conversely, transmission via the contact route was equally efficient at 30°C and 20°C. Our data imply that contact or short-range spread predominates in the tropics and offer an explanation for the lack of a well-defined, recurrent influenza season affecting tropical and subtropical regions of the world.
Herpes Simplex Virus Virion Host Shutoff Attenuates Establishment of the Antiviral State
Authors: Pasieka Tracy Jo , Lu Betty , Crosby Seth D. , Wylie Kristine M. , Morrison Lynda A. , Alexander Diane E. , Menachery Vineet D. , Leib David A.
Published: March 2008

Herpes simplex virus mutants lacking the vhs protein are severely attenuated in animal models of pathogenesis and exhibit reduced growth in primary cell culture. As a result of these properties, viruses withvhsdeleted have been proposed as live-attenuated vaccines. Despite these findings and their implications for vaccines, the mechanisms by which vhs promotes infection in cell culture and in vivo are not understood. In this study we demonstrate that vhs-deficient viruses replicate to reduced levels in interferon (IFN)-primed cells and that this deficit has both IFN-dependent and IFN-independent components. Furthermore, vhs-defective viruses induce increased and physiologically active levels of IFN, increased amounts of IFN-stimulated transcripts, and more phosphorylated eIF2α. In addition, we demonstrate greater accumulation of viral RNAs following infection with a vhs-deficient virus. This leads to the hypothesis that attenuation of viruses lacking vhs may be attributed to increased levels of double-stranded RNA, a potent pathogen-associated molecular pattern. Together these data show that vhs likely functions to reduce innate immune responses and thereby acts as a critical determinant of viral pathogenesis.
Hantaviruses Direct Endothelial Cell Permeability by Sensitizing Cells to the Vascular Permeability Factor VEGF, while Angiopoietin 1 and Sphingosine 1-Phosphate Inhibit Hantavirus-Directed Permeability
Authors: Gavrilovskaya Irina N. , Gorbunova Elena E. , Mackow Natalie A. , Mackow Erich R.
Published: March 2008

Hantaviruses infect human endothelial cells and cause two vascular permeability-based diseases: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Hantavirus infection alone does not permeabilize endothelial cell monolayers. However, pathogenic hantaviruses inhibit the function of αvβ3 integrins on endothelial cells, and hemorrhagic disease and vascular permeability deficits are consequences of dysfunctional β3 integrins that normally regulate permeabilizing vascular endothelial growth factor (VEGF) responses. Here we show that pathogenic Hantaan, Andes, and New York-1 hantaviruses dramatically enhance the permeability of endothelial cells in response to VEGF, while the nonpathogenic hantaviruses Prospect Hill and Tula have no effect on endothelial cell permeability. Pathogenic hantaviruses directed endothelial cell permeability 2 to 3 days postinfection, coincident with pathogenic hantavirus inhibition of αvβ3 integrin functions, and hantavirus-directed permeability was inhibited by antibodies to VEGF receptor 2 (VEGFR2). These studies demonstrate that pathogenic hantaviruses, similar to αvβ3 integrin-deficient cells, specifically enhance VEGF-directed permeabilizing responses. Using the hantavirus permeability assay we further demonstrate that the endothelial-cell-specific growth factor angiopoietin 1 (Ang-1) and the platelet-derived lipid mediator sphingosine 1-phosphate (S1P) inhibit hantavirus directed endothelial cell permeability at physiologic concentrations. These results demonstrate the utility of a hantavirus permeability assay and rationalize the testing of Ang-1, S1P, and antibodies to VEGFR2 as potential hantavirus therapeutics. The central importance of β3 integrins and VEGF responses in vascular leak and hemorrhagic disease further suggest that altering β3 or VEGF responses may be a common feature of additional viral hemorrhagic diseases. As a result, our findings provide a potential mechanism for vascular leakage after infection by pathogenic hantaviruses and the means to inhibit hantavirus-directed endothelial cell permeability that may be applicable to additional vascular leak syndromes.
Smoking rates among gamblers at Nevada casinos mirror US smoking rate
Authors: Pritsos C A , Pritsos K L , Spears K E
Published: March 2008

Objectives:

To determine the percentage of gamblers who smoke while gambling at three of Nevada’s major gambling destinations, Las Vegas, Reno/Sparks and Lake Tahoe.

Methods:

Teams of two people counted the number of smokers and total number of gamblers at various Nevada casinos. The total number of gamblers observed smoking was then multiplied by three to determine the total number of smokers. This methodology for determining the number of smokers in a room was established by Repace and Lowry in 1980.

Results:

We observed a total of 14 052 gamblers at the three sites, of which a total of 947 were smoking. We estimated the percentage of smokers at three gaming tourist centres in Nevada (Las Vegas, Reno/Sparks and Lake Tahoe). The percentage of smokers at Las Vegas (20.3% (95% CI 0.9)) and Reno/Sparks (21.5% (95% CI 1.2%)) did not significantly differ from the US population percentage of smokers (20.9% (95% CI 0.6%)) (p>0.05). However, at Lake Tahoe the percentage of smokers (16.4% (95% CI 1.8%)) was significantly lower than the published US population smoker percentage (p<0.0001). Mean percentage of smokers by location did not significantly differ (p = 0.43)

Conclusions:

The results of this study suggest that the percentage of gamblers who smoke was less than or not different from the overall US percentage of a population who smoke. These findings provide additional evidence to refute the exemption to smoking bans for casinos based upon the supposition that a greater percentage of casino customers are smokers than the general population and therefore a smoking ban for casinos may result in an economic hardship.
Stigma as Related to Mental Disorders
Authors: Hinshaw Stephen P. , Stier Andrea
Published: March 2008

Individuals with mental illness receive harsh stigmatization, resulting in decreased life opportunities and a loss of independent functioning over and above the impairments related to mental disorders themselves. We begin our review with a multidisciplinary discussion of mechanisms underlying the strong propensity to devalue individuals displaying both deviant behavior and the label of mental illness. Featured is the high potential for internalization of negative perceptions on the part of those with mental disorders—i.e., self-stigmatization. We next focus on several issues of conceptual and practical relevance: (a) stigma against less severe forms of mental disorder; (b) the role of perceptions of dangerousness related to mental illness; (c) reconciliation of behavioral research with investigations of explicit and implicit attitudes; (d) evolutionary models and their testability; (e) attributional accounts of the causes of mental illness, especially to personal control versus biogenetic factors; and (f) developmental trends regarding stigma processes. We conclude with a brief review of multilevel efforts to overcome mental illness stigma, spanning policy and legislation, alterations in media depictions, changed attitudes and practices among mental health professionals, contact and empathy enhancement, and family and individual treatment.
Anti-Inflammatory Actions of Intravenous Immunoglobulin
Authors: Nimmerjahn Falk , Ravetch Jeffrey V.
Published: March 2008

The remarkable success story of the therapeutic application of pooled immunoglobulin G (IgG) preparations from thousands of donors, the so-called intravenous IgG (IVIG) therapy, to patients with a variety of hematological and immunological disorders began more than half a century ago. Since then, the use of this primary blood product has increased constantly, resulting in the serious danger of shortages in supply. Despite its widespread use and therapeutic success, the mechanisms of action, especially of the anti-inflammatory activity, are only beginning to be understood. In this review, we summarize the clinical use of IVIG for different diseases and discuss recent data on the molecular mechanisms that might explain how this potent drug mediates its activity in vivo.
Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure
Authors: Borghi-Silva Audrey , Carrascosa Cláudia , Oliveira Cristino Carneiro , Barroco Adriano C. , Berton Danilo C. , Vilaça Debora , Lira-Filho Edgar B. , Ribeiro Dirceu , Nery Luiz Eduardo , Neder J. Alberto
Published: March 2008

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 ± 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Δ%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation ( P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation ( P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Δ[O2Hb]% and Δ[HbTOT]%, respectively ( P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.
Telokin expression and the effect of hypoxia on its phosphorylation status in smooth muscle cells from small and large pulmonary arteries
Authors: Madden Jane A. , Dantuma Mark W. , Sorokina Elena A. , Weihrauch Dorothee , Kleinman Jack G.
Published: March 2008

Small pulmonary arteries (SPA), <500 μm diameter of the cat, constrict when exposed to hypoxia, whereas larger arteries (large pulmonary arteries; LPA), >800 μm diameter, show little or no response. It is unknown why different contractile responses occur within the same vascular bed, but activator or repressor proteins within the smooth muscle cell (SMC) can modify myosin phosphatase and myosin light chain kinase (MLCK), thereby influencing the phosphorylation state of myosin light chain (MLC) and ultimately, contraction. Telokin, a protein with a sequence identical to the COOH-terminal domain of MLCK, is expressed in smooth muscle where in its phosphorylated state it inhibits myosin phosphatase, binds to unphosphorylated myosin, and helps maintain smooth muscle relaxation. We measured telokin mRNA and telokin protein in smooth muscle from different diameter feline pulmonary arteries and sought to determine whether changes in the phosphorylation status of telokin and MLC occurred during hypoxia. In pulmonary arteries, telokin expression varied inversely with artery diameter, but cerebral arteries showed neither telokin protein nor telokin mRNA. Although telokin and MLC were distributed uniformly throughout the SPA muscle cell cytoplasm, they were not colocalized. During hypoxia, telokin dephosphorylated, and MLC became increasingly phosphorylated in SPA SMC, whereas in LPA SMC there was no change in either telokin or MLC phosphorylation. When LPA SMC were exposed to phenylephrine, MLC phosphorylation increased with no change in telokin phosphorylation. These results suggest that in SPA, phosphorylated telokin may help maintain relaxation under unstimulated conditions, whereas in LPA, telokin's function remains undetermined.
A possible role for hypoxia-induced apelin expression in enteric cell proliferation
Authors: Han Song , Wang Guiyun , Qi Xiang , Lee Heung M. , Englander Ella W. , Greeley George H.
Published: March 2008

Apelin is the endogenous ligand for the APJ receptor, and apelin and APJ are expressed in the gastrointestinal (GI) tract. Intestinal inflammation increases intestinal hypoxia-inducible factor (HIF) and apelin expression. Hypoxia and inflammation are closely linked cellular insults. The purpose of these studies was to investigate the influence of hypoxia on enteric apelin expression. Exposure of rat pups to acute hypoxia increased hepatic, stomach-duodenal, and colonic apelin mRNA levels 10-, 2-, and 2-fold, respectively ( P < 0.05 vs. controls). Hypoxia also increased colonic APJ mRNA levels, and apelin treatment during hypoxia exposure enhanced colonic APJ mRNA levels further. In vitro hypoxia also increased apelin and APJ mRNA levels. The hypoxia-induced elevation in apelin expression is most likely mediated by HIF, since HIF-activated apelin transcriptional activity is dependent on an intact, putative HIF binding site in the rat apelin promoter. Acute exposure of rat pups to hypoxia lowered gastric and colonic epithelial cell proliferation; hypoxia in combination with apelin treatment increased epithelial proliferation by 50%. In vitro apelin treatment of enteric cells exposed to hypoxia increased cell proliferation. Apelin treatment during normoxia was ineffective. Our studies imply that the elevation in apelin expression during hypoxia and inflammation in the GI tract functions in part to stimulate epithelial cell proliferation.
Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2
Authors: Sala-Rabanal Monica , Loo Donald D. F. , Hirayama Bruce A. , Wright Ernest M.
Published: March 2008

The human proton/oligopeptide cotransporters hPEPT1 and hPEPT2 have been targeted to enhance the bioavailability of drugs and prodrugs. Previously, we established the mechanisms of drug transport by hPEPT1. Here, we extend these studies to hPEPT2. Major variants hPEPT2*1 and hPEPT2*2 were expressed in Xenopus oocytes, and each was examined using radiotracer uptake and electrophysiological methods. Glycylsarcosine (Gly-Sar); the β-lactam antibiotics ampicillin, amoxicillin, cephalexin, and cefadroxil; and the anti-neoplastics δ-aminolevulinic acid (δ-ALA) and bestatin induced inward currents, indicating that they are transported. Variations in transport rate were due to differences in affinity and in turnover rate: for example, cefadroxil was transported with higher apparent affinity but at a lower maximum velocity than Gly-Sar. Transport rates were highest at pH 5 and decreased significantly as the external pH was increased. Our results strongly suggest that the protein does not operate as a cotransporter in tissues where there is little or no pH gradient, such as choroid plexus, lung, or mammary gland. In the absence of substrates, rapid voltage jumps produced hPEPT2 capacitive currents at pH 7. These transients were significantly reduced at pH 5 but recovered on addition of substrates. The seven-state ordered kinetic model previously proposed for hPEPT1 accounts for the steady-state kinetics of neutral drug and dipeptide transport by hPEPT2. The model also explains the capacitive transients, the striking difference in pre-steady-state behavior between hPEPT2 and hPEPT1, and differences in turnover numbers for Gly-Sar and cefadroxil. No functional differences were found between the common variants hPEPT2*1 and hPEPT2*2.
Pharmacological blockade of B2-kinin receptor reduces renal protective effect of angiotensin-converting enzyme inhibition indb/dbmice model
Authors: Buléon Marie , Allard Julien , Jaafar Acil , Praddaude Françoise , Dickson Zara , Ranera Marie-Thérèse , Pecher Christiane , Girolami Jean-Pierre , Tack Ivan
Published: March 2008

Diabetic nephropathy (DN) can be delayed by the use of angiotensin-converting enzyme inhibitors (ACEi). The mechanisms of ACEi renal protection are not univocal. To investigate the impact of bradykinin B2receptor (B2R) activation during ACE inhibition, type II diabetic mice (C57BLKS db/db) received for 20 wk: 1) ACEi (ramipril) alone, 2) ACEi + HOE-140 (a specific B2R antagonist), 3) HOE-140 alone, or 4) no treatment. The development of DN, defined by an increase in albuminuria and glomerulosclerosis, was largely prevented by ACEi treatment (albuminuria: 980 ± 130 vs. 2,160 ± 330 mg/g creatinine; mesangial area: 22.5 ± 0.5 vs. 27.6 ± 0.3%). The protective effect of ramipril was markedly attenuated by B2R blockade (albuminuria: 2,790 ± 680 mg/g creatinine; mesangial area: 30.4 ± 1.1%), whereas HOE-140 alone significantly increased albuminuria. Despite such benefits, glomerular filtration rate remained unchanged, probably because of the combination of the hypotensive effect of diabetes in this model and the renal hemodynamic action of ramipril. Finally, the renal protective effect of ACEi was associated with a marked decrease in glomerular overexpression of insulin-like growth factor-1 (IGF-1) and transforming growth factor-β pathways, but also in advanced glycation end product receptors and lipid peroxidation assessed by 4-hydroxy-2-nonenal (4-HNE) adducts. Concomitant blockade of B2R partly restored glomerular overexpression of IGF-1 receptor β and 4-HNE complexes. These results support the critical role of B2R activation in the mediation of ACEi renal protection against DN and provide the rationale to examine the benefit of B2R activation by itself as a new therapeutic approach for DN.
Measurement of hemoglobin oxygen saturation using Raman microspectroscopy and 532-nm excitation
Authors: Torres Filho Ivo P. , Terner James , Pittman Roland N. , Proffitt Elizabeth , Ward Kevin R.
Published: March 2008

The resonant Raman enhancement of hemoglobin (Hb) in the Q band region allows simultaneous identification of oxy- and deoxy-Hb. The heme vibrational bands are well known at 532 nm, but the technique has never been used to determine microvascular Hb oxygen saturation (So2) in vivo. We implemented a system for in vivo noninvasive measurements of So2. A laser light was focused onto areas of 15–30 μm in diameter. Using a microscope coupled to a spectrometer and a cooled detector, Raman spectra were obtained in backscattering geometry. Calibration was performed in vitro using blood at several Hb concentrations, equilibrated at various oxygen tensions. So2 was estimated by measuring the intensity of Raman signals (peaks) in the 1,355- to 1,380-cm−1 range (oxidation state marker band ν4), as well as from the ν19 and ν10 bands (1,500- to 1,650-cm−1 range). In vivo observations were made in microvessels of anesthetized rats. Glass capillary pathlength and Hb concentration did not affect So2 estimations from Raman spectra. The Hb Raman peaks observed in blood were consistent with earlier Raman studies using Hb solutions and isolated cells. The correlation between Raman-based So2 estimations and So2 measured by CO-oximetry was highly significant for ν4, ν10, and ν19 bands. The method allowed So2 determinations in all microvessel types, while diameter and erythrocyte velocity could be measured in the same vessels. Raman microspectroscopy has advantages over other techniques by providing noninvasive and reliable in vivo So2 determinations in thin tissues, as well as in solid organs and tissues in which transillumination is not possible.
Spectral Analyses Reveal the Presence of Adult-Like Activity in the Embryonic Stomatogastric Motor Patterns of the Lobster,Homarus americanus
Authors: Rehm Kristina J. , Taylor Adam L. , Pulver Stefan R. , Marder Eve
Published: March 2008

The stomatogastric nervous system (STNS) of the embryonic lobster is rhythmically active prior to hatching, before the network is needed for feeding. In the adult lobster, two rhythms are typically observed: the slow gastric mill rhythm and the more rapid pyloric rhythm. In the embryo, rhythmic activity in both embryonic gastric mill and pyloric neurons occurs at a similar frequency, which is slightly slower than the adult pyloric frequency. However, embryonic motor patterns are highly irregular, making traditional burst quantification difficult. Consequently, we used spectral analysis to analyze long stretches of simultaneous recordings from muscles innervated by gastric and pyloric neurons in the embryo. This analysis revealed that embryonic gastric mill neurons intermittently produced pauses and periods of slower activity not seen in the recordings of the output from embryonic pyloric neurons. The slow activity in the embryonic gastric mill neurons increased in response to the exogenous application of Cancer borealis tachykinin-related peptide 1a (CabTRP), a modulatory peptide that appears in the inputs to the stomatogastric ganglion (STG) late in larval development. These results suggest that the STG network can express adult-like rhythmic behavior before fully differentiated adult motor patterns are observed, and that the maturation of the neuromodulatory inputs is likely to play a role in the eventual establishment of the adult motor patterns.
Conceptual Flexibility in the Human Brain: Dynamic Recruitment of Semantic Maps from Visual, Motor, and Motion-related Areas
Authors: Hoenig Klaus , Sim Eun-Jin , Bochev Viktor , Herrnberger Bärbel , Kiefer Markus
Published: March 2008

Traditionally, concepts are assumed to be situational invariant mental knowledge entities (conceptual stability), which are represented in a unitary brain system distinct from sensory and motor areas (amodality). However, accumulating evidence suggests that concepts are embodied in perception and action in that their conceptual features are stored within modality-specific semantic maps in the sensory and motor cortex. Nonetheless, the first traditional assumption of conceptual stability largely remains unquestioned. Here, we tested the notion of flexible concepts using functional magnetic resonance imaging and event-related potentials (ERPs) during the verification of two attribute types (visual, action-related) for words denoting artifactual and natural objects. Functional imaging predominantly revealed crossover interactions between category and attribute type in visual, motor, and motion-related brain areas, indicating that access to conceptual knowledge is strongly modulated by attribute type: Activity in these areas was highest when nondominant conceptual attributes had to be verified. ERPs indicated that these category-attribute interactions emerged as early as 116 msec after stimulus onset, suggesting that they reflect rapid access to conceptual features rather than postconceptual processing. Our results suggest that concepts are situational-dependent mental entities. They are composed of semantic features which are flexibly recruited from distributed, yet localized, semantic maps in modality-specific brain regions depending on contextual constraints.
Mirror Neuron System Differentially Activated by Facial Expressions and Social Hand Gestures: A Functional Magnetic Resonance Imaging Study
Authors: Montgomery Kimberly J. , Haxby James V.
Published: March 2008

Facial expressions and hand gestures are utilized in nonverbal communication to convey socially relevant information. One key process that mediates nonverbal communication is simulation. The mirror neuron system (MNS), which maps observed actions onto the motor representations used when producing those actions, likely plays a role in simulation. Previous neuroimaging experiments have identified a putative human MNS that includes the inferior parietal lobule (IPL) and the frontal operculum. Although understanding nonverbal communication presumably involves the MNS, it is unknown whether these two forms of nonverbal social communication have distinct representations within that system. Here we report the results of a functional magnetic resonance imaging experiment in which participants viewed, imitated, and produced facial expressions and social hand gestures. The observation and execution of facial expressions and social hand gestures activated the MNS, but the magnitude of response differed. Activation in the IPL was greater for social hand gestures, whereas activation in the frontal operculum was greater for viewing facial expressions. The locations of neural activity evoked by viewing facial expressions and social hand gestures in the frontal operculum were significantly different. These data argue that there are distinct representations of different types of social nonverbal communication in the MNS.
The Evolution of Illustrated Texts and Their Effect on Science: Examples from Early American State Geological Reports
Authors: Johnson Carol Siri
Published: March 2008

In the 19th century, printing methods made significant advances that allowed mass production of illustrated texts; prior to that time, illustrated texts were expensive and rare. The number of illustrated texts thus rose exponentially, increasing the rate of information transfer among scientists, engineers and the general public. The early American state geological reports, funded by the state legislatures, were among the pioneering volumes that used the new graphic capabilities in the improved printing processes for the advancement of science. They contain thousands of illustrations—woodcuts, etchings, lithographs and hand-painted maps—that may be of interest to historians of science, technology, art and culture.
Gordon Pask: Cybernetic Polymath
Authors: Fernández María
Published: March 2008

Despite his influence in art, architecture and theater, British cybernetician Gordon Pask is rarely acknowledged in histories of digital culture and virtually unknown in the history of art. Pask is better known as a theoretician than as an artist or designer, although his machines, artwork and theories were closely related. This article investigates the relevance of specific aspects of Pask's theories to his best-known artwork, The Colloquy of Mobiles, to illustrate his characteristic unification of science and art, and theory and material experimentation. Select works of contemporary art are discussed to indicate Pask's significance to contemporary art practices.
'Riddled' with Guilt: The Mysteries of Transgression, the Sealed Vision, and the Art of Interpretation in 4Q300 and Related Texts
Authors: Thomas Samuel
Published: March 2008

This essay investigates the language of 4Q300, one of the manuscripts of the 'Mysteries' composition from caves 1 and 4 (1Q27, 4Q299–300[1]), for the way in which it participates in the 'prophetic-sapiential' dynamic of Qumran apocalypticism. Though 4Q300 may not have been authored by a member of the Qumran community, it expresses ideas and assumes social categories very much at home within a sectarian context. It presumes a dualistic framework in which the in-group possesses knowledge of 'mysteries' that derives from having access to a 'vision.' This vision is sealed to the opponents, the 'magicians' whose failed interpretations render them 'guilty' of not understanding the true 'root of wisdom.' The essay argues that this 'vision' is best understood to be a written source that is considered by the author/audience of 4Q300 to have prophetic implications.
Midlatitude Static Stability in Simple and Comprehensive General Circulation Models
Authors: Frierson Dargan M. W.
Published: March 2008

The static stability of the extratropical troposphere is examined in two atmospheric general circulation models (GCMs) over idealized boundary conditions, with emphasis on the role of moisture in determining the midlatitude stability. The determination of the static stability is compared within two models: an idealized moist model with simplified representations of radiative transfer and other physical processes, and a comprehensive GCM with full physics. The GCMs are run over a zonally symmetric, fixed sea surface temperature (SST) aquaplanet surface, with a multitude of SST distributions to study the response of the extratropical static stability over a wide parameter range.

In both models, the dry static stability averaged over the midlatitudes increases both with increases in the meridional temperature gradients, and with increases in the mean SST. These changes in static stability are compared with both moist theories and dry theories. Dry baroclinic eddy theories are invalid for the entire parameter range in the idealized GCM, and for much of the parameter range considered in the comprehensive GCM. A moist theory, on the other hand, works remarkably well in predicting the midlatitude stability over the entire parameter range for both models. These simulations give strong support for the influence of moisture on the thermal structure of the midlatitudes.
A Generalization of Lorenz’s Model for the Predictability of Flows with Many Scales of Motion
Authors: Rotunno R. , Snyder C.
Published: March 2008

In a seminal paper, E. N. Lorenz proposed that flows with many scales of motion in which smaller-scale error spreads to larger scales and in which the error-doubling time decreases with decreasing scale have a finite range of predictability. Although the Lorenz theory of limited predictability is widely understood and accepted, the model upon which the theory is based is less so. The primary objection to the model is that it is based on the two-dimensional vorticity equation (2DV) while simultaneously emphasizing results using a basic turbulent flow with a “−5/3” energy spectrum in the atmospheric synoptic scale instead of those using a more theoretically and observationally consistent “−3” spectrum. The present work generalizes the Lorenz model so that it may apply to the surface quasigeostrophic equations (SQGs), which are mathematically very similar to 2DV but are known to have a −5/3 kinetic energy spectrum downscale from a large-scale forcing. This generalized Lorenz model is applied here to both 2DV (with a −3 spectrum) and SQG (with a −5/3 spectrum), producing examples of flows with unlimited and limited predictability, respectively. Comparative analysis of the two models allows for the identification of the distinctive attributes of a many-scaled flow with limited predictability.
Impact of Saharan Dust on Tropical North Atlantic SST*
Authors: Foltz Gregory R. , McPhaden Michael J.
Published: March 2008

A combination of satellite and in situ datasets is used to investigate the impact of interannual changes in atmospheric dust content on the sea surface temperature (SST) of the tropical North Atlantic Ocean. Throughout most of the region the authors find, in agreement with previous studies, that positive anomalies of dust are associated with a significant reduction in surface shortwave radiation (SWR), while negative anomalies of dust are associated with an enhancement of SWR. Statistical analysis for 1984–2000 suggests that changes in dustiness in the tropical North Atlantic (10°–25°N, 20°–60°W) explained approximately 35% of the observed interannual SST variability during boreal summer, when climatological dust concentrations are highest. Measurements from a long-term moored buoy in the central tropical North Atlantic are used to investigate the causes of anomalously cool SST that occurred in conjunction with a period of enhanced dustiness at the start of the unexpectedly quiet 2006 hurricane season. It is found that surface SWR varied out of phase with dustiness, consistent with historical analyses. However, most of the anomalous cooling occurred prior to the period of enhanced dustiness and was driven primarily by wind-induced latent heat loss, with horizontal oceanic heat advection and SWR playing secondary roles. These results indicate that dust-induced changes in SWR did not play a major direct role in the cooling that led up to the 2006 Atlantic hurricane season.
Large-Scale Oceanographic Constraints on the Distribution of Melting and Freezing under Ice Shelves
Authors: Little Christopher M. , Gnanadesikan Anand , Hallberg Robert
Published: March 2008

Previous studies suggest that ice shelves experience asymmetric melting and freezing. Topography may constrain oceanic circulation (and thus basal melt–freeze patterns) through its influence on the potential vorticity (PV) field. However, melting and freezing induce a local circulation that may modify locations of heat transport to the ice shelf. This paper investigates the influence of buoyancy fluxes on locations of melting and freezing under different bathymetric conditions. An idealized set of numerical simulations (the “decoupled” simulations) employs spatially and temporally fixed diapycnal fluxes. These experiments, in combination with scaling considerations, indicate that while flow in the interior is governed by large-scale topographic gradients, recirculation plumes dominate near buoyancy fluxes. Thermodynamically decoupled models are then compared to those in which ice–ocean heat and freshwater fluxes are driven by the interior flow (the “coupled” simulations). Near the southern boundary, strong cyclonic flow forced by melt-induced upwelling drives inflow and melting to the east. Recirculation is less evident in the upper water column, as shoaling of meltwater-freshened layers dissipates the dynamic influence of buoyancy forcing, yet freezing remains intensified in the west. In coupled simulations, the flow throughout the cavity is relatively insensitive to bathymetry; stratification, the slope of the ice shelf, and strong, meridionally distributed buoyancy fluxes weaken its influence.
Corporate Social Performance Disoriented: Saving the Lost Paradigm?
Authors: Gond Jean-Pascal , Crane Andrew
Published: March 2008

Corporate social performance (CSP) has been a prominent concept in the management literature dealing with the social role and impacts of the corporation; it has been promulgated as a unifying paradigm for the field. However, the concept of CSP is still lacking strong theoretical foundations and empirical validity, suggesting that the paradigmatic status of CSP might be lost. In this paper, the authors draw on Hirsch and Levin’s (1999) life cycle approach to explore the development of CSP as a concept, explain why it has so recurrently failed to deliver on these dimensions, and offer possible routes for future research that may potentially ameliorate this problem.