bluuebunny/crossref_metadata_2025 huggingface dataset:
ECOLOGICAL COSTS ON LOCAL ADAPTATION OF AN INSECT HERBIVORE IMPOSED BY HOST PLANTS AND ENEMIES
Authors: Zovi Daniel , Stastny Michael , Battisti Andrea , Larsson Stig
Published: May 2008

Herbivore populations may become adapted to the defenses of their local hosts, but the traits that maximize host exploitation may also carry ecological costs. We investigated the patterns and costs of local adaptation in the pine processionary moth, Thaumetopoea pityocampa, to its host plants, Pinus nigra and P. sylvestris. The two hosts differ in needle toughness, a major feeding impediment for leaf‐eating insects. We observed a west‐to‐east gradient of increasing progeny size in the Italian Alps, matching the pattern in toughness of their respective local host plant. Eastern populations that feed on the native P. nigra with tough needles had larger eggs, and neonate larvae with larger head capsules, than western populations that feed on the native P. sylvestris and the introduced P. nigra with softer foliage. In a reciprocal transfer experiment that involved the eastern‐most and the western‐most populations of T. pityocampa from this region, and excluded natural enemies, we found evidence for local adaptation to the host plant. Specifically, larvae from the western population only performed well when raised on their local hosts with soft needles, and they suffered near‐complete mortality on the tough foliage at the eastern site. In contrast, larvae from the eastern population survived equally well at both sites. Local adaptation involved a trade‐off between progeny size and the number of offspring. We hypothesized that an additional cost, imposed by natural enemies, may be associated with increased egg size: we also observed a west‐to‐east gradient of increased egg parasitism. We tested this hypothesis in a common garden by exposing eggs of both populations to parasitism by two native egg parasitoids, Ooencyrtus pityocampae and Baryscapus servadeii. The eastern population suffered a higher level of parasitoid attack by O. pityocampae than the western population, and performance of hatched adults of both parasitoids was enhanced in large eggs. Thus, increased neonate quality (larger eggs yielding larger larvae) confers an advantage on tough foliage but incurs the ecological cost of increased parasitism, which may constrain further adaptation by this herbivore.
DENSITY‐MEDIATED, CONTEXT‐DEPENDENT CONSUMER–RESOURCE INTERACTIONS BETWEEN ANTS AND EXTRAFLORAL NECTAR PLANTS
Authors: Chamberlain Scott A. , Holland J. Nathaniel
Published: May 2008

Interspecific interactions are often mediated by the interplay between resource supply and consumer density. The supply of a resource and a consumer's density response to it may in turn yield context‐dependent use of other resources. Such consumer–resource interactions occur not only for predator–prey and competitive interactions, but for mutualistic ones as well. For example, consumer–resource interactions between ants and extrafloral nectar (EFN) plants are often mutualistic, as EFN resources attract and reward ants which protect plants from herbivory. Yet, ants also commonly exploit floral resources, leading to antagonistic consumer–resource interactions by disrupting pollination and plant reproduction. EFN resources associated with mutualistic ant–plant interactions may also mediate antagonistic ant–flower interactions through the aggregative density response of ants on plants, which could either exacerbate ant–flower interactions or alternatively satiate and distract ants from floral resources. In this study, we examined how EFN resources mediate the density response of ants on senita cacti in the Sonoran Desert and their context‐dependent use of floral resources. Removal of EFN resources reduced the aggregative density of ants on plants, both on hourly and daily time scales. Yet, the increased aggregative ant density on plants with EFN resources decreased rather than increased ant use of floral resources, including contacts with and time spent in flowers. Behavioral assays showed no confounding effect of floral deterrents on ant–flower interactions. Thus, ant use of floral resources depends on the supply of EFN resources, which mediates the potential for both mutualistic and antagonistic interactions by increasing the aggregative density of ants protecting plants, while concurrently distracting ants from floral resources. Nevertheless, only certain years and populations of study showed an increase in plant reproduction through herbivore protection or ant distraction from floral resources. Despite pronounced effects of EFN resources mediating the aggregative density of ants on plants and their context‐dependent use of floral resources, consumer–resource interactions remained largely commensalistic.
CONDITION‐DEPENDENT INDIVIDUAL DECISION‐MAKING DETERMINES CYPRINID PARTIAL MIGRATION
Authors: Brodersen Jakob , Nilsson P. Anders , Hansson Lars-Anders , Skov Christian , Brönmark Christer
Published: May 2008

Partial migration is a common phenomenon among many animals and occurs in many types of ecosystems. Understanding the mechanisms behind partial migration is of major importance for the understanding of population dynamics and, eventually, ecosystem processes. We studied the effects of food availability on the seasonal partial migration of cyprinid fish from a lake to connected streams during winter by the use of passive telemetry. Fish with increased access to food were found to migrate in higher proportion, earlier in the season, and to reside in the streams for a longer period compared to fish with decreased access to food. Furthermore, fewer unfed migrants returned to the lake, indicating higher overwinter mortality. Our results suggest that individual fish trade off safety from predation and access to food differently depending on their body condition, which results in a condition‐dependent partial migration. Hence, our main conclusion is that individual decision‐making is based on assessment of own condition which offers a mechanistic explanation to partial migration. Moreover, this may be of high importance for understanding population responses to environmental variation as well as ecosystem dynamics and stability.
DEMOGRAPHY OF THE ENDEMIC MINT DICERANDRA FRUTESCENS IN FLORIDA SCRUB
Authors: Menges Eric S.
Published: May 2008

Florida scrub supports many endemic species in a pyrogenic shrubland on xeric yellow sands. One genus with multiple endemics is the mint Dicerandra, with its five narrowly endemic species most prevalent in edges and recently burned areas. Study of the demography of Dicerandra frutescens, an endemic and endangered mint restricted to Florida scrub, began in September 1988. Eleven populations have been studied at various locations across Archbold Biological Station and at one privately held site. Some populations, particularly along fire lanes, have been added during the study. Survival and recruitment data were initially collected monthly but were later collected quarterly in September, December, March, and June. Each annual census in September also recorded the life history stage for that “year” (the year including any censuses after the prior September census) and measures of size (basal diameter, number of branch tips, number of reproductive branch tips). Survival variables representing monthly, quarterly, and annual survival were also assembled. These survival variables contain information on the type of plant recruiting (seedling or new adult) or, for plants already in the data set, whether the plant survived the interval, died during the interval, was already (previously) dead, or whether survival could not be ascertained (no tag, no plant).

Several populations were subjected to prescribed burns during the study. For years with burns, variables summarize whether plants (or quadrats) were burned or not. This data set consists of 5530 records, each an individual plant, from 1988 through 2004. Published analyses based on data from 1990–2000 found that finite rates of increase were greater than 1 for populations less than six years post‐fire, but thereafter populations were predicted to decline. Similarly, populations in fire lanes were most successful when the time‐since‐disking was short. A yard‐edge population showed variable demography. Stochastic simulations in Florida scrub sites suggested an optimal fire return interval of 6–12 years (regular fires) or 6–21 years (stochastic fires).

Data collection on this project is continuing, and we anticipate updating data periodically.
“Under Construction”
Authors: Peoples Whitney A.
Published: May 2008

This essay seeks to explore the sociopolitical objectives of hip-hop feminism, to address the generational ruptures that those very objectives reveal, and to explore the practical and theoretical qualities that second- and third-wave generations of black feminists have in common. Ultimately, the goal of this essay is to clearly understand the sociopolitical platform of hip-hop feminists and how that platform both impacts and figures into the history and future of black American feminist thought.
“Like an Old Soul Record”
Authors: Clay Andreana
Published: May 2008

Examinations of the relationship of queer sexuality and the hip-hop generation have recently emerged in academia. However, little or no work has been done that explores hip-hop's bisexual, independent poster child, Me'Shell Ndegeocello. Since her debut in 1993, Ndegeocello's relationship to hip-hop has been both a reflection of and influence upon understandings of race, gender, and sexuality for a generation of queer feminists of color. In this paper, I examine how her emergence and popularity mark an important political and ideological moment for queer Black women in the post-civil rights era. Grounded in the works of Patricia Hill Collins, bell hooks, Audre Lorde, and Jewelle Gomez, I examine how media representations of Ndegeocello coupled with her lyrics and music demonstrate the complexities and contradictions of “hip-hop feminism.” In particular, the 1990s represent a movement away from the Reagan/Bush era that characterized not only the teenage years of hip-hop culture, but important cultural and economic advances of the Black community. At the same time, this decade marks the shift to the more “liberal” Clinton administration, where the advances of previous generations began to decline. In this context I ask in what ways does Me'Shell Ndegeocello represent a generation of young queer women who were raised after (and sometimes on) early Black feminist critique? Further, how is her work emblematic of Black feminist understandings of gender and sexuality at the same time that she complicates this same discourse?
Identification of Staphylococcal Enterotoxin B Domains Involved in Binding to Cultured Human Kidney Proximal Tubular Cells: Imparting Proliferation and Death
Authors: Chatterjee Subroto , Neill Roger , Shupp Jeffrey W. , Hammamieh Rasha , Ionin Boris , Jett Marti
Published: May 2008

Studies suggest that staphylococcal enterotoxin B (SEB) is initially harbored in the kidney by binding to digalactosylceramide molecules in the proximal tubular cells. However, little is known in regard to the peptide motif within SEB that binds to these cells and imparts toxic effects. Herein, using human kidney proximal tubular cells (PTs) we have performed a systematic study on the binding of various peptides and peptide analogs of SEB and demonstrate a structure-functional relationship. Using [125I]labeled SEB peptides, we show a high affinity and displaceable binding of SEB 191–220 to human PT cells. Binding was mitigated by the use of antibody against SEB, by digalactosylceramide (the putative receptor), and by the use of endoglycoceramidase, which selectively removes the oligosaccharide backbones from glycosphingolipids. Our structure/ functional studies revealed that peptide 130–160 induces a concentration-dependent increase in programmed cell death/ apoptosis in human proximal tubular cells. Mechanistic studies further suggest that SEB/SEB peptide (130–160) impart apoptosis via the activation of neutral sphingomyelinase, which hydrolizes sphingomyelin to ceramide and phosphocholine. SEB 130–160 mediated apoptosis was mitigated by preincubation of cells with antibody against SEB and an SEB 130–160 antibody.
Effects of Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) Hull Extracts on the Secretion of Progesterone and Estradiol In Vivo and In Vitro
Authors: Hsia Shih-Min , Yeh Chih-Lan , Kuo Yueh-Hsiung , Wang Paulus S. , Chiang Wenchang
Published: May 2008

Adlay ( Coix lachryma-jobi L. var. ma-yuen Stapf.) has been used as a traditional Chinese medicine for dysfunction of the endocrine system. However, there have been few studies on the effects of adlay seed on the endocrine system. In the present study, both the in vivo and in vitro effects of methanolic extracts of adlay hull (AHM) on progesterone synthesis were studied. AHM was partitioned with four different solvents: water, 1-butanol, ethyl acetate, and n-hexane. Four fractions, namely, AHM-Wa (water fraction), AHM-Bu (1-butanol fraction), AHM-EA (ethyl acetate fraction), and AHM-Hex ( n-hexane fraction), were respectively obtained. Granulosa cells (GCs) were prepared from pregnant mare serum gonadotropin-primed immature female rats and were challenged with different reagents, including human chorionic gonadotropin (hCG; 0.5 IU/ml), 8-bromo-adenosine-3′,5′-cyclic monophosphate (8-Br-cAMP; 0.1 m M), forskolin (10 μ M), 25-OH-cholesterol (10 μ M), and pregnenolone (10 μ M), in the presence or absence of AHM (100 μg/ml). The functions of steroidogenic enzymes, including protein expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage enzyme (P450scc), protein kinase A (PKA), and aromatase activity, were investigated. The expression of StAR mRNA was also explored by using real-time reverse transcription–polymerase chain reaction. In the in vivo study, AHM decreased plasma progesterone and estradiol levels after an intravenous injection of AHM (2 mg/ ml/kg). In the in vitro studies, AHM decreased progesterone and estradiol via inhibition of (i) the cAMP-PKA signal transduction pathway, (ii) cAMP accumulation, (iii) P450scc and 3β-HSD enzyme activities, (iv) PKA, P450scc and StAR protein expressions and StAR mRNA expression, and (v) aromatase activity in rat GCs. These results suggest that AHM decreased the production of progesterone via mechanisms involving the inhibition of the cAMP pathway, enzyme activities, and the protein expressions of P450scc and StAR in rat GCs.
Poly(ADP-Ribose) Polymerase Inhibition Improves Endothelial Dysfunction Induced by Hypochlorite
Authors: Radovits Tamás , Zotkina Julia , Lin Li-Ni , Bömicke Timo , Arif Rawa , Gerö Domokos , Horváth Eszter M. , Karck Matthias , Szabó Csaba , Szabó Gábor
Published: May 2008

Reactive oxygen species, such as myeloperoxidase-derived hypochlorite, induce oxidative stress and DNA injury. The subsequent activation of the DNA-damage–poly(ADP-ribose) polymerase (PARP) pathway has been implicated in the pathogenesis of various diseases, including ischemia-reperfusion injury, circulatory shock, diabetic complications, and atherosclerosis. We investigated the effect of PARP inhibition on the impaired endothelium-dependent vasorelaxation induced by hypochlorite. In organ bath experiments for isometric tension, we investigated the endothelium-dependent and endothelium-independent vasorelaxation of isolated rat aortic rings using cumulative concentrations of acetylcholine and sodium nitro-prusside. Endothelial dysfunction was induced by exposing rings to hypochlorite (100–400 μ M). In the treatment group, rings were preincubated with the PARP inhibitor INO-1001. DNA strand breaks were assessed by the TUNEL method. Immunohistochemistry was performed for 4-hydroxynonenal (a marker of lipid peroxidation), nitrotyrosine (a marker of nitrosative stress), and poly(ADP-ribose) (an enzymatic product of PARP). Exposure to hypochlorite resulted in a dose-dependent impairment of endothelium-dependent vasorelaxation of aortic rings, which was significantly improved by PARP inhibition, whereas the endothelium-independent vasorelaxation remained unaffected. In the hypochlorite groups we found increased DNA breakage, lipidperoxidation, and enhanced nitrotyrosine formation. The hypochloride-induced activation of PARP was prevented by INO-1001. Our results demonstrate that PARP activation contributes to the pathogenesis of hypochlorite-induced endothelial dysfunction, which can be prevented by PARP inhibitors.
Fetal Learning About Ethanol and Later Ethanol Responsiveness: Evidence Against “Safe” Amounts of Prenatal Exposure
Authors: Abate Paula , Pueta Mariana , Spear Norman E. , Molina Juan C.
Published: May 2008

Near-term fetuses of different mammalian species, including humans, exhibit functional sensory and learning capabilities. The neurobiological literature indicates that the unborn organism processes sensory stimuli present in the amniotic fluid, retains this information for considerable amounts of time, and is also capable of associating such stimuli with biologically relevant events. This research has stimulated studies aimed at the analysis of fetal and neonatal learning about ethanol, a topic that constitutes the core of the present review. Ethanol has characteristic sensory (olfactory, taste, and trigeminal) attributes and can exert pharmacologic reinforcing effects. The studies under examination support the hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol. These levels of prenatal ethanol exposure do not generate evident morphologic or neurobehavioral alterations in the offspring, but they exert a significant impact upon later ethanol-seeking and intake behaviors. Supported by preclinical and clinical findings, this review contributes to strengthening the case for the ability of prenatal ethanol exposure to have effects on the postnatal organism.
Nitrosyl-Cobinamide, a New and Direct Nitric Oxide–Releasing Drug Effective In Vivo
Authors: Broderick Kate E. , Alvarez Luis , Balasubramanian Mahesh , Belke Darrell D. , Makino Ayako , Chan Adriano , Woods Virgil L. , Dillmann Wolfgang H. , Sharma Vijay S. , Pilz Renate B. , Bigby Timothy D. , Boss Gerry R.
Published: May 2008

A limited number of nitric oxide (NO)-generating drugs are available for clinical use for acute and chronic conditions. Most of these agents are organic nitrates, which do not directly release NO; tolerance to the drugs develops, in part, as a consequence of their conversion to NO. We synthesized nitrosyl-cobinamide (NO-Cbi) from cobinamide, a structural analog of cobalamin (vitamin B12). NO-Cbi is a direct NO-releasing agent that we found was stable in water, but under physiologic conditions, it released NO with a half-life of 30 mins to 1 h. We show in five different biological systems that NO-Cbi is an effective NO-releasing drug. First, in cultured rat vascular smooth muscle cells, NO-Cbi induced phosphorylation of vasodilator-stimulated phosphoprotein, a downstream target of cGMP and cGMP-dependent protein kinase. Second, in isolated Drosophila melanogaster Malpighian tubules, NO-Cbi–stimulated fluid secretion was similar to that stimulated by Deta-NONOate and a cGMP analog. Third, in isolated mouse hearts, NO-Cbi increased coronary flow much more potently than nitroglycerin. Fourth, in contracted mouse aortic rings, NO-Cbi induced relaxation, albeit to a lesser extent than sodium nitroprusside. Fifth, in intact mice, a single NO-Cbi injection rapidly reduced blood pressure, and blood pressure returned to normal after 45 mins; repeated NO-Cbi injections induced the expected fall in blood pressure. These studies indicate that NO-Cbi is a useful NO donor that can be used experimentally in the laboratory; moreover, it could be developed into a vasodilating drug for treating hypertension and potentially other diseases such as angina and congestive heart failure.
A BRIEF COMMUNICATION
Authors: Wolff George L. , Stanley J. Steven , Ferguson Matthew E. , Simpson Pippa M. , Ronis Martin J. J. , Badger Thomas M.
Published: May 2008

Enhanced linear growth, hyperplasia, and tumorigenesis are well-known characteristics of “viable yellow” agouti Avy/- mice (Wolff GL, Roberts DW, Mountjoy KG. Physiol Genomics 1:151–163, 1999); however, the functional basis for this aspect of the phenotype is unknown. In the present study, we ascertained whether agouti signaling protein (ASIP) levels in Avy/a or a/a livers are associated with hepatocyte proliferation as a possible factor in promotion of hepatocellular tumor formation. Proliferating cell nuclear antigen (PCNA) assays and quantitative real-time reverse transcriptase polymerase chain reaction assays were performed on liver samples from mottled yellow Avy/a, pseudoagouti Avy/a, and black a/a VY mice to determine mitotic indices and expression levels of Avyand a in relation to the expression level of the housekeeping gene hprt. We found that ASIP levels were ~100-fold higher in yellow than in pseudoagouti or black mice and that the proportion of PCNA-positive hepatocytes was greater ( P < 0.001) in yellow than in pseudoagouti or black mice.
Physically Active Lifestyle Enhances Vagal-Cardiac Function but Not Central Autonomic Neural Interaction in Elderly Humans
Authors: Shi Xiangrong , Schaller Frederick A. , Tierney Nancy , Chanthavong Patrick , Chen Shande , Raven Peter B. , Smith Michael L.
Published: May 2008

The cause of the age-related impairment of arterial baroreflex function remains ill-defined; moreover, it is unknown whether this impairment results from aging per se or from an inactive lifestyle associated with aging. In this study, we sought to: 1) determine whether elderly individuals who maintained an active lifestyle had an enhanced carotid baroreflex function as compared with their sedentary counterparts; and 2) determine whether this difference was due in part to altered function of the arterial baroreceptor and/or altered central modulation. Eight healthy, sedentary (SED, 68 ± 2 yr) and eight physically active (ACT, 68 ± 1 yr) elderly men with peak O2 consumption 25.5 ± 1.2 vs 35.7 ± 2.4 ml/min/kg (P < 0.01), respectively, were assessed with carotid baroreceptor (CBR) function using 5s pulses of neck pressure or suction (ranging from +40 to −80 Torr) delivered to the carotid sinus region at rest and during lower body negative pressure (LBNP) of −15 and −40 Torr. Changes in heart rate (HR) and mean arterial pressure (MAP) were assessed for CBR-HR and CBR-MAP gains, respectively. Overall CBR-HR gains in a range of ∼ 120 mmHg of carotid sinus pressure were greater (P < 0.01) in ACT than SED at rest and during LBNP. The derived peak CBR-HR slopes between ACT and SED at rest were −0.32 ± 0.07 vs −0.11 ± 0.02 bpm/mmHg (P = 0.007), respectively. However, there was no statistical difference (P = 0.37) in CBR-MAP gains between the groups. Neither CBR-MAP (P = 0.08) nor CBR-HR (P = 0.41) gain was augmented by LBNP in the elderly. Conclusion: Active lifestyle enhances the CBR-HR reflex sensitivity as a result of the improved vagal-cardiac function in elderly people. Aging is associated with an absence of central autonomic interaction in the control of blood pressure regardless of physical fitness.
Effect of a High-Intensity Exercise Training on the Metabolism and Function of Macrophages and Lymphocytes of Walker 256 Tumor–Bearing Rats
Authors: Bacurau Aline Villa Nova , Belmonte Mônica Aparecida , Navarro Francisco , Moraes Milton Rocha , Pontes Francisco Luciano , Pesquero Jorge Luiz , Araújo Ronaldo Carvalho , Bacurau Reury Frank Pereira
Published: May 2008

Epidemiologic studies suggest that moderately intense training promotes augmented immune function, whereas strenuous exercise can cause immunosupression. Because the combat of cancer requires high immune function, high-intensity exercise could negatively affect the host organism; however, despite the epidemiologic data, there is a lack of experimental evidence to show that high-intensity training is harmful to the immune system. Therefore, we tested the influence of high-intensity treadmill training (10 weeks, 5 days/week, 30 mins/day, 85% VO2max) on immune system function and tumor development in Walker 256 tumor–bearing Wistar rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, in addition to some functional parameters such as hydrogen peroxide production, phagocytosis, and lymphocyte proliferative responses. The metabolism of Walker 256 cells was also investigated. Results demonstrated that high-intensity training increased the life span of tumor-bearing rats, promoted a reduction in tumor mass, and prevented indicators of cachexia. Several changes, such as a reduction in body weight and food intake and activation of glutamine metabolism in macrophages and lymphocytes induced by the presence of Walker 256 tumor, were prevented by high intensity training. The reduction in tumor growth was associated with an impairment of tumor cell glucose and glutamine metabolism. These data suggest that high-intensity exercise training may be a viable strategy against tumors.
A BRIEF COMMUNICATION
Authors: Holt David C. , Fedinec Alexander L. , Vaughn Ashley N. , Leffler Charles W.
Published: May 2008

In newborn pigs, carbon monoxide (CO) contributes to regulation of cerebrovascular circulation. Results from isolated adult cerebral arteries suggest CO may have less dilatory potential in mature animals. However, few data are available on the direct effects of CO on cerebrovascular circulation in vivo except for those from newborn pigs. Therefore, we tested the hypothesis that i) rat cerebral arterioles dilate to CO in vivo and ii) CO-induced cerebrovascular dilatory responses are age dependent in pigs. Also, we examined whether the permissive role of nitric oxide in CO-induced dilation observed in piglets is present in older pigs and rats. Experiments used anesthetized newborn, 7-week-old, and juvenile (3- to 4-month-old) pigs and 3- to 4-month-old rats with closed cranial windows and topical applications of CO and sodium nitroprusside (SNP). Dilations to SNP were not different at different ages in pigs or between pigs and rats. CO produced pial arteriolar dilations in all groups. Dilation to 10−5 M CO was reduced in juvenile pigs as compared to newborn and 7-week-old pigs, and tended to less at 10−6 M CO. Dilations of rat pial arterioles to all concentrations were less than those of newborn and 7-week-old pigs, but not different from those of juvenile pig pial arterioles. In newborn and 7-week-old pigs, l-nitro-arginine (LNA) inhibited the dilation to CO, an effect reversed by a constant background of SNP. In contrast, LNA did not reduce dilation to CO in juvenile pigs or rats. In conclusion, rat pial arterioles like those in piglets dilate to CO in vivo, but there are age and species differences with regard to reactivity and interaction with NO.
5′-AMP-Activated Protein Kinase Signaling in Caenorhabditis elegans
Authors: Beale Elmus G.
Published: May 2008

5′-AMP-activated protein kinase (AMPK) has been called “the metabolic master switch” because of its central role in regulating fuel homeostasis. AMPK, a heterotrimeric serine/threonine protein kinase composed of α, β, and γ subunits, is activated by upstream kinases and by 5′-AMP in response to various nutritional and stress signals. Downstream effects include regulation of metabolism, protein synthesis, cell growth, and mediation of the actions of a number of hormones, including leptin. However, AMPK research represents a young and growing field; hence, there are many unanswered questions regarding the control and action of AMPK. This review presents evidence for the existence of AMPK signaling pathways in Caenorhabditis elegans, a genetically tractable model organism that has yet to be fully exploited to elucidate AMPK signaling mechanisms.
Polygoni Cuspidati Radix Inhibits the Activation of Syk Kinase in Mast Cells for Antiallergic Activity
Authors: Lim Beong Ou , Lee Jun Ho , Ko Na Young , Mun Se Hwan , Kim Jie Wan , Kim Do Kyun , Kim Ju Dong , Kim Bo Kyung , Kim Hyung Sik , Her Erk , Lee Hoi Young , Choi Wahn Soo
Published: May 2008

The antiallergic activity of Polygoni cuspidati radix (PR) and the mechanism of action by which it functions were investigated in this study. The extract of PR exhibited potent inhibitory activity in mast cells; its IC50 values were 62 ± 2.1 μg/ml for RBL-2H3 mast cells and 46 ± 3.2 μg/m for bone marrow–derived mast cells by antigen stimulation, and it also suppressed the expression of tumor necrosis factor-α and interleukin-4 in RBL-2H3 cells. According to the in vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis, in a dose-dependent manner. With regard to its mechanism of action, PR inhibited the activating phosphorylation of Syk, a key signaling protein for the activation of mast cells. It also suppressed Akt and the mitogen-activated protein kinases ERK1/2, p38, and JNK, which are critical for the production of various inflammatory cytokines in mast cells. The results of the study indicate that the antiallergic activity of PR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk activating phosphorylation in mast cells.
The Acute Proinflammatory and Prothrombotic Effects of Pulmonary Exposure to Rutile TiO2Nanorods in Rats
Authors: Nemmar Abderrahim , Melghit Khaled , Ali Badreldin H.
Published: May 2008

Nanotechnology is extensively used in industry and is widely explored for possible applications in medicine. However, its potential respiratory and systemic adverse effects remain unknown. Here pure titanium dioxide (TiO2) nanorods with rutile structure were prepared at room temperature by using a soft chemistry technique. The structure of the TiO2rutile nanorods was confirmed by powder X-ray diffraction, and the size was revealed by transmission electron microscopy. Thereafter, we investigated, in Wistar rats, the acute (24-hr) effects of intratracheal instillation of these rutile TiO2nanorods (1 and 5 mg/kg) on lung inflammation (assessed by bronchoalveolar lavage), systemic inflammation, and platelet aggregation in whole blood. Compared with vehicle-exposed rats, rats that underwent intratracheal instillation of TiO2nanorods experienced a dose-dependent increase in macrophage numbers at 1 (+50%) and 5 mg/kg (+81%; P < 0.05) and an influx of neutrophils at 1 (+294%) and 5 mg/kg (+4117%; P < 0.01) in their bronchoalveolar lavage fluid. Both doses of rutile TiO2nanorods caused pulmonary and cardiac edema, assessed by analysis of the wet weight–to–dry weight ratios. Similarly, the numbers of monocytes and granulocytes in the blood were increased in a dose-dependent manner after exposure to rutile TiO2nanorods. In contrast, the number of platelets was significantly reduced after pulmonary exposure to 5 mg/kg TiO2nanorods; this result indicated the occurrence of platelet aggregation in vivo. The direct addition of TiO2nanorods (0.4–10 μg/ml) to untreated rat blood significantly induced platelet aggregation in a dose-dependent fashion in vitro. It is concluded that the intratracheal instillation of rutile TiO2nanorods caused upregulation of lung inflammation, pulmonary and cardiac edema, and systemic inflammation. Rutile TiO2nanorods also triggered platelet aggregation in vivo and in vitro.
PPARα Mediates Transcriptional Upregulation of Novel Organic Cation Transporters-2 and -3 and Enzymes Involved in Hepatic Carnitine Synthesis
Authors: Koch Alexander , König Bettina , Stangl Gabriele I. , Eder Klaus
Published: May 2008

We tested the hypothesis that transcription of novel organic cation transporters (OCTNs) is directly regulated by peroxisome proliferator–activated receptor (PPAR)-α. Therefore, wild-type mice and mice deficient in PPARα (PPARα−/−) were treated with the PPARα agonist WY 14,643. Wild-type mice treated with WY 14,643 had a greater abundance of OCTN2 mRNA in their liver, muscle, kidney, and small intestine and a greater abundance of OCTN3 mRNA in kidney and small intestine than did untreated wild-type mice ( P < 0.05). Moreover, wild-type mice treated with WY 14,643 had greater mRNA abundances of enzymes involved in hepatic carnitine synthesis (4-N-trimethylaminobutyraldehyde dehydrogenase, γ-butyrobetaine dioxygenase) and increased carnitine concentrations in liver and muscle than did untreated wild-type mice ( P < 0.05). Untreated PPARα−/−mice had a lower abundance of OCTN2 mRNA in liver, kidney, and small intestine and lower carnitine concentrations in plasma, liver, and kidney than did untreated wild-type mice ( P < 0.05). In PPARα−/−mice, treatment with WY 14,643 did not influence mRNA abundance of OCTN2 and OCTN3 and carnitine concentrations in all tissues analyzed. The abundance of OCTN1 mRNA in all the tissues analyzed was not changed by treatment with WY 14,643 in wild-type or PPARα−/−mice. In conclusion, this study shows that transcriptional upregulation of OCTN2 and OCTN3 in tissues and of enzymes involved in hepatic carnitine biosynthesis are mediated by PPARα. It also shows that PPARα mediates changes of whole-body carnitine homeostasis in mice by upregulation of carnitine transporters and enzymes involved in carnitine synthesis.
Alternate Hypothesis on the Pathogenesis of Dengue Hemorrhagic Fever (DHF)/Dengue Shock Syndrome (DSS) in Dengue Virus Infection
Authors: Noisakran Sansanee , Perng Guey Chuen
Published: May 2008

Dengue fever, caused by infection with dengue virus, is not a new disease, but recently because of its serious emerging health threats, coupled with possible dire consequences including death, it has aroused considerable medical and public health concerns worldwide. Today, dengue is considered one of the most important arthropod-borne viral diseases in humans in terms of morbidity and mortality. Globally, it is estimated that approximate 50 to 100 million new dengue virus infections occur annually. Among these, there are 200,000 to 500,000 cases of potential life-threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), characterized by thrombocytopenia and increased vascular permeability. The death rate associated with the more severe form DHF/DSS is approximately 5%, predominantly in children under the age of 15. Although intensive efforts have been made to study the early clinical pathophysiology of dengue infection with the objective to identify the potential cause of DHF, results or data that have accumulated from different regions of the world involving studies of different ethnicity groups are inconsistent at present in terms of identifying a unified hypothesis for the pathogenesis of DHF/DSS. Thus, the potential mechanisms involved in the pathogenesis of DHF and DSS remain elusive. The purpose of this review is to identify alternate factors, such as innate immune parameters, hyper-thermal factors, conditioning of neutralizing antibody, concept of vector transmission, and physical status of virus in viremic patients that may play a role in the induction of DHF and DSS, which might have directly or indirectly contributed to the discrepancies that are noted in the literature reported to date. It is the hope that identification of an alternative explanation for the pathogenesis of DHF/DSS will pave the way for the institution of new strategies for the prevention of this complicated disease.
Promoting Collaborations Between Biomedical Scholars in the U.S. and Sub-Saharan Africa
Authors: Glew Robert H.
Published: May 2008

The premise of this piece is that a priority of international health should be to increase the number of investigators in the US and other developed countries who engage in research and other kinds of scholarly work in underdeveloped parts of the world, particularly sub-Saharan Africa where the overall disease burden is the highest and the gap in biomedical research infrastructure is the widest. The author’s aim is to encourage medical students, resident doctors, and medical school faculty to devote a part of their career to teach, acquire clinical skills, or participate in research with health professionals at teaching hospitals in Africa. After briefly describing the thinking that led the author to Nigeria 30 years ago to teach and study biochemical aspects of health problems in rural and urban areas, he discusses some of the factors one needs to consider before entering into an international partnership, including identifying the right foreign collaborators, selecting a suitable research site, setting realistic goals, learning the local culture and indigenous language, and defining a theme for your program. Lastly, the piece points out potential pitfalls and problems that are often overlooked or underestimated in the early phases of planning an international partnership, including lukewarm institutional support at home, inflexible institutional review boards, dominance of the program by the US partner, maintaining continuity, and striking the right balance between scholarly work and humanitarian efforts. My hope is that US students and faculty in the health professions who read this piece will be stimulated and encouraged to consider how they might integrate into their curriculum or academic life visits lasting several months or more each year during which they would teach or train others or engage in research at a teaching hospital in some country in Africa.
Chemoprevention of Arylamine-Induced Colorectal Aberrant Crypts
Authors: Feng Yi , Neale Jason R. , Doll Mark A. , Hein David W.
Published: May 2008

Since recombinant human cyclooxygenase (COX) enzymes have been shown to activate environmental and dietary carcinogens implicated in human colorectal cancer etiology, we hypothesized that COX-2 inhibitors reduce arylamine-induced aberrant crypts (AC) and foci (ACF), preneoplastic lesions of colorectal cancer. Male weanling F344 inbred rats were fed modified AIN-76A control diet or the same diets supplemented with 320 ppm sulindac or 500, 1000, or 1500 ppm celecoxib. At 7 weeks of age, rats received a subcutaneous injection of 3,2′-dimethyl-4-aminobiphenyl (DMABP), an aryl-amine colon carcinogen, once weekly for two weeks. Ten weeks after the initial DMABP or vehicle treatment (at 17 weeks of age), rats were euthanized with CO2, and the entire colorectum was removed and scored for ACF and AC. ACF possessing one to five AC were identified in the colorectum of rats administered DMABP, whereas no AC/ACF were identified in vehicle-treated controls. Significant reductions (p < 0.001) in ACF and AC frequencies were observed in DMABP-treated rats supplemented with sulindac or celecoxib. Celecoxib reduced AC and ACF more than sulindac, but this difference was not significant (p > 0.05). Reductions in both AC and ACF were highest following treatment with 1000 ppm celecoxib. These results provide additional experimental support for the chemopreventive effects of COX inhibitors in arylamine-induced colorectal cancer.
An Integrated Strategy in Two-Dimensional Electrophoresis Analysis Able to Identify Discriminants Between Different Clinical Conditions
Authors: Pattini Linda , Mazzara Saveria , Conti Antonio , Iannaccone Sandro , Cerutti Sergio , Alessio Massimo
Published: May 2008

Two-dimensional gel electrophoresis (2DE) is an indispensable tool in proteomics for the analysis of protein expression in complex biological systems such as cells and tissues. However, the automatic extraction of information from gel images is still a challenging task. In this paper we propose a strategy that represents a computational procedure of support to the discrimination of different clinical conditions associated with the samples. The analyzed gel images were acquired within the framework of a study of peripheral neuropathies: twenty-four 2DE maps generated from cerebrospinal fluid (16 pathologic and 8 control subjects) were processed. Quantitative features were defined to describe each image and treated with a method of dimensionality reduction. The informativeness of the descriptors allowed us to see the gel of the data set as items in a three-dimensional space, segregating according to the clinical conditions. Moreover, information with prognostic value was obtained for a single outsider gel of a patient who was included in a clinical subgroup at the first diagnosis but whose disease progressed with clinical features belonging to a different clinical subgroup. The method developed may represent an effective tool of classification that can be used repeatedly to capture the essential impression from separation images.
The Investigation of the Antioxidative Properties of the Novel Synthetic Organoselenium Compounds in Some Rat Tissues
Authors: Selamoglu Talas Zeliha , Ozdemir Ilknur , Yilmaz Ismet , Gok Yetkin , Orun Ibrahim
Published: May 2008

DMBA (7,12-dimethylbenz[a]anthracene) is a polycyclic aromatic hydrocarbon (PAH) known to cause tumors in rats. Selenium is an essential element with physiological non-enzymatic antioxidant properties. Because of the health problems induced by many environmental pollutants, many efforts have been undertaken in evaluating the relative antioxidant potential of selenium and synthetic organoselenium compounds. In this study, adult female Wistar rats were treated with DMBA and the novel organoselenium compounds (1- isopropyl-3-methylbenzimidazole-2-selenone [SeI] and 1,3-di- p-methoxybenzylpyrimidine-2-selenone [SeII]) in the determined doses. The protective effects of novel synthetic organoselenium compounds (SeI and SeII) against DMBA-induced changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and total glutathione (GSH) and malone-dialdehyde (MDA) levels of rat heart and brain were investigated. It was determined that SeI and SeII fully or partially restored enzyme activity. It was also found that lipid peroxidation was also decreased in SeI and SeII treated groups. Consequently, it was determined that novel synthetic organoselenium compounds (SeI and SeII) provided protection of antioxidant activity, and protection against lipid peroxidation measured as MDA in SeI and SeII treated groups was provided by novel synthesized organoselenium compounds. The ability of the organoselenium compounds to prevent oxidative damage induced by DMBA in rats was rationalized.
Influence of Lifelong Soy Isoflavones Consumption on Bone Mass in the Rat
Authors: Mardon J. , Mathey J. , Kati-Coulibaly S. , Puel C. , Davicco M.-J. , Lebecque P. , Horcajada M.-N. , Coxam V.
Published: May 2008

Soy isoflavones (IFs) have shown a bone-sparing effect through epidemiological studies in the Asian population. However, there is no evidence as to whether such protection would result from a lifelong exposure. We investigated the impact of an early exposure to IFs on bone status. Sixty female Wistar rats were fed either a standard diet ( n = 30) or the same food enriched with IFs (0.87 mg/g of diet) ( n = 30). After 1 month, they were allowed to mate, and were kept on the same regimen during the whole gestation and lactation periods. At weaning, female pups were each assigned to one of four nutritional groups; within each experimental group, animals were split into two groups, fed either the standard or the IF-rich diet. At 2, 3, 6, 12, 18, and 24 months after birth, 10 animals in each group were sacrificed. Femurs were collected for mechanical testing and bone mineral density (BMD) measurement. The rats perinatally or lifelong exposed to the IF-rich diet exhibited higher body weight and fat mass at 24 months of age. Peak bone mass was achieved between 6 and 12 months and did not differ between groups. In animals perinatally exposed to IF, BMD continued to increase. Thus, at 24 months, femoral total BMD ( P < 0.05), metaphyseal BMD ( P < 0.01), and failure load ( P < 0.05) were higher in the offspring born from mothers provided IF during pregnancy. Postnatal exposure alone did not improve bone parameters. This experiment provides evidence that perinatal exposure to phytoestrogens leads to a higher BMD later in life. It is suggested that these changes may have occurred as a consequence of programming effects, as has been shown for the endocrine and immune systems.
Cytokine and Chemokine Expression Associated with Steatohepatitis and Hepatocyte Proliferation in Rats Fed Ethanol via Total Enteral Nutrition
Authors: Ronis Martin J. J. , Butura Angelica , Korourian Soheila , Shankar Kartik , Simpson Pippa , Badeaux Jamie , Albano Emanuele , Ingelman-Sundberg Magnus , Badger Thomas M.
Published: May 2008

To determine the temporal relationship between alcohol-induced changes in cytokines and chemokines, development of liver pathology and stimulation of hepatocyte proliferation, male Sprague-Dawley rats were intragastrically fed low carbohydrate-containing ethanol (EtOH) diets via total enteral nutrition (TEN) for up to 49 d. Induction of EtOH metabolism and appearance of steatosis preceded development of oxidative stress, inflammation, and cell death. A transitory peak of tumor necrosis factor (TNFα) and interferon gamma (IFNγ) was observed at 14 d followed by reduced expression of TNFα, IFNγ and another Th1 cytokine IL-12 accompanied by reduced expression of the Th1 regulators T-bet and STAT4. After 35–49 d of EtOH, at a time when hepatocyte proliferation was stimulated, IL-12 returned to control values and a second peak of TNFα occurred. The Th2 cytokine IL-4 remained suppressed throughout the study and was accompanied by reductions in the Th2 regulator GATA3. There was no temporal effect of EtOH on expression of IL-6 or TGFβ. IL-5 and IL-13 mRNA were undetectable. Chemokine CXCL-2 expression increased progressively up to 35 d and preceded the appearance of inflammatory infiltrates. These data suggest that steatosis, increased ethanol metabolism, a transient induction of the innate immune response and suppression of Th2 responses were acute consequences of ethanol treatment and were followed by suppression of Th1 responses. However, the majority of necrosis, apoptosis and a late peak of TNFα only occurred after 6–7 weeks of ethanol, coincided with the appearance of inflammatory infiltrates and were associated with stimulation of hepatocyte proliferation.
Propofol Depresses Angiotensin II–Induced Cardiomyocyte Hypertrophy In Vitro
Authors: Zou Xiao-Jing , Yang Le , Yao Shang-Long
Published: May 2008

Cardiomyocyte hypertrophy is formed in response to pressure or volume overload, injury, or neurohormonal activation. The most important vascular hormone that contributes to the development of hypertrophy is angiotensin II (Ang II). Accumulating studies have suggested that reactive oxygen species (ROS) may play an important role in cardiac hypertrophy. Propofol is a general anesthetic that possesses antioxidant action. We therefore examined whether propofol inhibited Ang II–induced cardiomyocyte hypertrophy. Our results showed that both ROS formation and hypertrophic responses induced by Ang II in cardiomyocytes were partially blocked by propofol. Further studies showed that propofol inhibited the phophorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2) induced by Ang II via a decrease in ROS production. In addition, propofol also markedly attenuated Ang II–stimulated nuclear factor-κB (NF-κB) activation via a decrease in ROS production. In conclusion, propofol prevents cardiomyocyte hypertrophy by interfering with the generation of ROS and involves the inhibition of the MEK/ERK signaling transduction pathway and NF-κB activation.