bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Range Self Calibrating Velocity Selector
Authors: Grosser Arthur E.
Published: February 2005

A slotted disk type velocity selector which transmits a velocity selected beam when rotating in either a clockwise (``forward'') or counterclockwise (``reverse'') sense has been constructed and tested. The selector has two ranges: high velocity (1880 m/sec at 30 000 rpm) with low resolution (19.2%), and low velocity (940 m/sec at 30 000 rpm) with high resolution (7.2%). The calibration of the selector is performed without reference to any of the properties of the molecular beam used in the calibration procedure.
Microscope for Observing Magneto-Optic Rotation at Low Temperatures
Authors: Carroll K. J. , Liebenberg D. H. , Overton W. C.
Published: February 2005

A description is given of simple modifications of a standard laboratory research microscope which provide it with built-in parallel, monochromatic plane polarized specimen illumination. The converted microscope has been used, along with a Faraday glass technique, to obtain improved resolution in studies of the intermediate state of superconductors.
Pioneer VI Detector to Measure Degree of Anisotropy of Cosmic Radiation in Energy Range 7.5–90 MeV/Nucleon
Authors: Bartley W. C. , McCracken K. G. , Rao U. R.
Published: February 2005

An instrument designed to measure the degree of anisotropy of the cosmic radiation in the energy range 7.5–90 MeV/nucleon with an accuracy of better than one part in 104 is described. The instrument has been flown on the interplanetary spacecraft Pioneer VI and VII, and the in-flight performance and, in particular, the in-flight calibration procedures are briefly reviewed.
Surface enrichment of branched polymers in linear hosts: Effect of asymmetry in intersegmental interactions and density gradients
Authors: Minnikanti Venkatachala S. , Archer Lynden A.
Published: February 2005

Variable density lattice treatment of surface enrichment of f-arm star-branched chains in star/linear polymer blends is compared with results of an analytical response theory proposed by Wu and Fredrickson [Macromolecules 29, 7919 (1996)]. We find that differences in treating the intersegmental interactions in the small interfacial region near a free surface lead to significant differences in the potentials by which polymer chain ends are attracted towards the surface. Consideration of an asymmetric relationship between segment potentials and density changes in polystyrene at 450K and 0.1MPa, for example, gives typically a threefold to fourfold enhancement in composition of star molecules at a vacuum interface. When contributions from gradients in density are included in the analysis even greater levels of surface enhancement (fivefold to sixfold increases) are observed. By appropriately estimating the attraction of chain ends and repulsion of branch points at a free surface, we show that concentration profiles of branched polymers predicted in the lattice model are consistent with results obtained in the analytical response theory.
Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain
Authors: Ubuka Takayoshi , Bentley George E. , Ukena Kazuyoshi , Wingfield John C. , Tsutsui Kazuyoshi
Published: February 2005

We recently identified a novel hypothalamic neuropeptide inhibiting gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). Cell bodies and terminals containing the dodecapeptide GnIH are localized in the paraventricular nucleus (PVN) and median eminence, respectively. To understand the physiological role of GnIH, we investigated the mechanisms that regulate GnIH expression. In this study, we show that melatonin originating from the pineal gland and eyes induces GnIH expression in the quail brain. Pinealectomy (Px) combined with orbital enucleation (Ex) (Px plus Ex) decreased the expression of GnIH precursor mRNA and content of mature GnIH peptide in the diencephalon, which includes the PVN and median eminence. Melatonin administration to Px plus Ex birds caused a dosedependent increase in expression of GnIH precursor mRNA and production of mature peptide. The expression of GnIH was photoperiodically controlled and increased under short-day photoperiods, when the duration of melatonin secretion increases. To identify the mode of melatonin action on GnIH induction, we investigated the expression of Mel1c, a melatonin receptor subtype, in GnIH neurons.In situhybridization of Mel1cmRNA combined with immunocytochemistry for GnIH revealed that Mel1cmRNA was expressed in GnIH-immunoreactive neurons in the PVN. Melatonin receptor autoradiography further revealed specific binding of melatonin in the PVN. These results indicate that melatonin is a key factor for GnIH induction. Melatonin appears to act directly on GnIH neurons through its receptor to induce GnIH expression. This is the first demonstration, to our knowledge, of a direct action of melatonin on neuropeptide induction in any vertebrate class.
Longer lifespan, altered metabolism, and stress resistance in
Drosophila
from ablation of cells making insulin-like ligands
Authors: Broughton Susan J. , Piper Matthew D. W. , Ikeya Tomoatsu , Bass Timothy M. , Jacobson Jake , Driege Yasmine , Martinez Pedro , Hafen Ernst , Withers Dominic J. , Leevers Sally J. , Partridge Linda
Published: February 2005

The insulin/insulin-like growth factor-like signaling pathway, present in all multicellular organisms, regulates diverse functions including growth, development, fecundity, metabolic homeostasis, and lifespan. In flies, ligands of the insulin/insulin-like growth factor-like signaling pathway, the
Drosophila
insulin-like peptides, regulate growth and hemolymph carbohydrate homeostasis during development and are expressed in a stage- and tissue-specific manner. Here, we show that ablation of
Drosophila
insulin-like peptide-producing median neurosecretory cells in the brain leads to increased fasting glucose levels in the hemolymph of adults similar to that found in diabetic mammals. They also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold. However, the ablated flies show an extension of median and maximal lifespan and increased resistance to oxidative stress and starvation.
Multiple homeostatic mechanisms in the control of P1 plasmid replication
Authors: Das Nilangshu , Valjavec-Gratian Majda , Basuray Ashish N. , Fekete Richard A. , Papp Peter P. , Paulsson Johan , Chattoraj Dhruba K.
Published: February 2005

Many organisms control initiation of DNA replication by limiting supply or activity of initiator proteins. In plasmids, such as P1, initiators are limited primarily by transcription and dimerization. However, the relevance of initiator limitation to plasmid copy number control has appeared doubtful, because initiator oversupply increases the copy number only marginally. Copy number control instead has been attributed to initiator-mediated plasmid pairing (“handcuffing”), because initiator mutations to handcuffing deficiency elevates the copy number significantly. Here, we present genetic evidence of a role for initiator limitation in plasmid copy number control by showing that autorepression-defective initiator mutants also can elevate the plasmid copy number. We further show, by quantitative modeling, that initiator dimerization is a homeostatic mechanism that dampens active monomer increase when the protein is oversupplied. This finding implies that oversupplied initiator proteins are largely dimeric, partly accounting for their limited ability to increase copy number. A combination of autorepression, dimerization, and handcuffing appears to account fully for control of P1 plasmid copy number.
Control of seed mass and seed yield by the floral homeotic gene
APETALA2
Authors: Jofuku K. Diane , Omidyar Pamela K. , Gee Zorana , Okamuro Jack K.
Published: February 2005

APETALA2
(
AP2
) is best known for its role in the regulation of flower meristem and flower organ identity and development in
Arabidopsis
. We show here that
AP2
also plays an important role in determining seed size, seed weight, and the accumulation of seed oil and protein. We demonstrate genetically that
AP2
acts through the maternal sporophyte and endosperm genomes to control seed weight and seed yield. Thus,
AP2
functions outside the boundaries of flower meristem and flower organ development to affect agronomically relevant traits in
Arabidopsis
.
Allele-Specific Assay Reveals Functional Variation in theChalcone SynthasePromoter ofArabidopsis thalianaThat Is Compatible with Neutral Evolution
Authors: de Meaux Juliette , Goebel Ulrike , Pop Ana , Mitchell-Olds Thomas
Published: February 2005

Promoters are thought to play a major role in adaptive evolution, yet little is known about the regulatory diversity within species, where microevolutionary processes take place. To investigate the potential for evolutionary change in the promoter of a gene, we examined nucleotide and functional variation of the Chalcone Synthase (CHS) cis-regulatory region in Arabidopsis thaliana. CHS is the branch point enzyme of a biosynthetic pathway that leads to the production of secondary metabolites influencing the interaction between the plant and its environment. We found that nucleotide diversity in the intergenic region encompassing the CHS promoter (π = 0.003) is compatible with neutral expectations. To quantify functional variation specifically as a result of cis-regulation of CHS mRNA levels, we developed an assay using F1 individuals in which distinct promoter alleles are compared within a common trans-regulatory background. We examined functional cis-regulatory variation in response to different stimuli representing a variety of CHS transcriptional environments (dark, light, and insect feeding). We observed extensive functional variation, some of which appeared to be independent of the trans-regulatory background. Comparison of functional and nucleotide diversity suggested a candidate point mutation that may explain cis-regulatory differences in light response. Our results indicate that functional changes in promoters can arise from a few mutations, pointing to promoter regions as a fundamental determinant of functional genetic variation.
Microstructures and Microwave Dielectric Characteristics of Ca(Zn1/3Nb2/3)O3 Complex Perovskite Ceramics
Authors: Chen X. M. , Liu D. , Hou R. Z. , Hu X. , Liu X. Q.
Published: February 2005

Ca(Zn1/3Nb2/3)O3 microwave dielectric ceramics were prepared using a solid‐state reaction process, and their microwave dielectric properties were evaluated as functions of sintering and postdensification annealing conditions. The relationship between microwave dielectric properties and processing was interpreted through the variation of microstructures. The dielectric constant showed slight variation with sintering and annealing conditions, but the Q×f value increased at first and then decreased with increased sintering temperature, and annealing in oxygen indicated significant improvement in Q×f, especially for the specimens sintered at higher temperatures. The good microwave dielectric properties were obtained in the ceramics sintered at 1225°C in air for 3 h and annealed at 1100°C in oxygen for 8 h: ɛ= 34.1, Q×f= 15 890 GHz, τf=−48 ppm/°C.
Language loss in Guatemala: A statistical analysis of the 1994 population census
Authors: Hawkins Richard John
Published: February 2005

This study examines several approaches linguists have taken to explain native language attrition. Five attitudinal factors linked to ethnolinguistic vitality are examined: minority status, access to, and participation in, institutions and markets, cultural strength, education, and migration. Each factor was quantified into proxy variables using information compiled from the 1994 Guatemalan national population census. After constructing the data set, the author used regression analysis of the proxy variables to determine the significance of each attitudinal factor. Minority status, participation in institutions and markets, education, and migration all showed statistically significant correlations with language attrition among Maya speakers in Guatemala. Cultural strength, however, did not show a statistically significant correlation to language loss in the country.
Molecular pathways in bladder cancer: Part 1
Authors: Bryan Richard T. , Hussain Syed A. , James Nicholas D. , Jankowski Janusz A. , Wallace D. Michael A.
Published: February 2005

This month, three of the mini‐reviews are descriptive of bladder cancer. The first two of these relate to various aspects of molecular pathways in bladder cancer. In this ever‐changing field, it is important to keep abreast of new information, and the authors from Birmingham do this for us in a way that is easy to understand and complete.

The third of these reviews assesses reports of non‐urothelial bladder tumours, a relatively uncommon subject. In this helpful article, the authors from Rennes classify and explain these tumours, which comprise ≈5% of bladder tumours.

Finally, authors from Cleveland classify the methods used for the diagnosis of seminal oxidative stress, sperm DNA damage and apoptosis, and the association of these with male fertility.
Incidence, prevalence and management of lower urinary tract symptoms in men in the UK
Authors: Logie John , Clifford Gary M. , Farmer Richard D.T.
Published: February 2005

OBJECTIVE

To describe the incidence, prevalence and management of lower urinary tract symptoms (LUTS), suggestive of benign prostatic hyperplasia, reported in UK general practice.

PATIENTS AND METHODS

All clinical information relating to LUTS and its treatment was assessed for men aged ≥ 45 years and registered on the UK General Practice Research Database (GPRD) at some time between 1992 and 2001. Incidence and prevalence were derived from the GPRD population. Secular trends in the management of LUTS were examined from prescribing rates and the intervals between first symptoms, first treatment and surgery or catheterization.

RESULTS

The incidence of reported LUTS showed a strong linear increase with age. The prevalence increased from 3.5% for men aged 45–49 years to > 30% for men aged > 85 years. Between 1992 and 2000 there was a five‐fold increase in the proportion of time with LUTS when men were receiving medical treatment. This was accompanied by a progressive decrease in the intervals between first symptoms and first drug treatment, and a significant increase in the intervals from first symptoms or first treatment to surgery or catheterization. Treated men received surgery or catheterization significantly later than those receiving no drug treatment.

CONCLUSION

There has been a significant increase in the use of medical therapy for LUTS over the last decade. The accompanying postponement of surgery/catheterization is likely to be a result, at least in part, of successful earlier medical treatment and the treatment of a greater proportion of symptomatic men.
The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia
Authors: Fitzpatrick John M. , Desgrandchamps François
Published: February 2005

The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients’ quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. á1‐Adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled‐release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross‐over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5á‐reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well‐tolerated, long‐term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.
The Relevance of Precautionary Saving
Authors: Ventura Luigi , Eisenhauer Joseph G.
Published: February 2005

This paper develops a model of personal saving that includes, unlike previous models appearing in the literature, an explicit role for the Leland-Kimball measure of prudence. Estimation of the model using Bank of Italy survey data suggests that about 20 per cent of total saving is driven by precautionary reasons.
Private Prayer and Civic Involvement
Authors: LOVELAND MATTHEW T. , SIKKINK DAVID , MYERS DANIEL J. , RADCLIFF BENJAMIN
Published: February 2005

We analyze the relationship between private prayer and participation in voluntary association. We argue that prayer fosters a cognitive connection to the needs of others, and thus promotes membership in associations that emphasize personal relationships. Private prayer is not related to membership in political groups. The effect of prayer is strengthened by membership in religious groups, suggesting the relevance of both organizational and devotional aspects of religion for civil society participation.
We Are a Religious People;  We Are a Vengeful People
Authors: GREER TAMMY , BERMAN MITCHELL , VARAN VALERIE , BOBRYCKI LORI , WATSON SHEREE
Published: February 2005

We evaluate the relation between religiousness and vengeance using multiple indicators of religiousness (religious orientation and church variables) and behavioral as well as self‐reports of vengeance. Results from hierarchical regression analyses revealed that intrinsic religious orientation was negatively and extrinsic religious orientation positively related to self‐reports of revenge but not to behavioral indicators of revenge. Only quest orientation was related to behavioral indicators of revenge with those higher on quest setting relatively lower levels of shock following a provocation and giving more money to an obnoxious confederate. Of the church variables, the number of religious activities was negatively and frequency of monetary donations positively related to self‐reported vengeance. Only frequency of monetary donations, however, was uniquely related to one of the behavioral indicators of revenge, level of shock, with those who give more frequently also retaliating with higher levels of shock.
Dynamics of skeletal muscle oxygenation during sequential bouts of moderate exercise
Authors: Ferreira Leonardo F. , Lutjemeier Barbara J. , Townsend Dana K. , Barstow Thomas J.
Published: February 2005

In rat muscle, faster dynamics of microvascular PO2 (approximately blood flow

to O2 uptake

ratio) after prior contractions that did not alter blood [lactate] have been considered to be a consequence of faster

kinetics. However, in humans, prior exercise below the lactate threshold does not affect the pulmonary

kinetics. To clarify this apparent discrepancy, we examined the effects of prior moderate exercise on the kinetics of muscle oxygenation (deoxyhaemoglobin, [HHb]α

) and pulmonary

in humans. Eight subjects performed two bouts (6 min each) of moderate‐intensity cycling separated by 6 min of baseline pedalling. Muscle (vastus lateralis) oxygenation was evaluated by near‐infrared spectroscopy and

was measured breath‐by‐breath. The time constant (τ) of the primary component of

was not significantly affected by prior exercise (21.5 ± 9.2 versus 25.6 ± 9.7 s; Bout 1 versus 2, P= 0.49). The time delay (TD) of [HHb] decreased (11.6 ± 2.6 versus 7.7 ± 1.5 s; Bout 1 versus 2, P < 0.05) and τ[HHb] increased (7.0 ± 3.5 versus 10.2 ± 4.6 s; Bout 1 versus 2, P < 0.05), while the mean response time (TD +τ) did not change (18.6 ± 2.7 versus 17.9 ± 3.9 s) after prior moderate exercise. Thus, prior moderate exercise resulted in shorter onset and slower rate of increase in [HHb] during subsequent exercise. These data suggest that prior exercise altered the dynamic interaction between

and

following the onset of exercise.
Surface Roughness Effects on External Heat Transfer of a HP Turbine Vane
Authors: Stripf M. , Schulz A. , Wittig S.
Published: February 2005

External heat transfer measurements on a highly loaded turbine vane with varying surface roughness are presented. The investigation comprises nine different roughness configurations and a smooth reference surface. The rough surfaces consist of evenly spaced truncated cones with varying height, diameter, and distance, thus covering the full range of roughness Reynolds numbers in the transitionally and fully rough regimes. Measurements for each type of roughness are conducted at several freestream turbulence levels (Tu1=4% to 8.8%) and Reynolds numbers, hereby quantifying their combined effect on heat transfer and laminar-turbulent transition. In complementary studies a trip wire is used on the suction side in order to fix the transition location close to the stagnation point, thereby allowing a deeper insight into the effect of roughness on the turbulent boundary layer. The results presented show a strong influence of roughness on the onset of transition even for the smallest roughness Reynolds numbers. Heat transfer coefficients in the turbulent boundary layer are increased by up to 50% when compared to the smooth reference surface.
Murine Gammaherpesvirus 68 Open Reading Frame 11 Encodes a Nonessential Virion Component
Authors: Boname Jessica M. , May Janet S. , Stevenson Philip G.
Published: February 2005

Open reading frame 11 (ORF11) is a conserved gammaherpesvirus gene that remains undefined. We identified the product of murine gammaherpesvirus 68 (MHV-68) ORF11, p43, as a virion component with a predominantly perinuclear distribution in infected cells. MHV-68 lacking p43 grew normally in vitro but showed reduced lytic replication in vivo and a delay in seeding to the spleen. Subsequent latency amplification was normal. Thus, MHV-68 ORF11 encoded a virion component that was important for in vivo lytic replication but dispensable for the establishment of latency.
REGULATION OF PHOSPHORUS HOMEOSTASIS BY THE TYPE IIA NA/PHOSPHATE COTRANSPORTER
Authors: Tenenhouse Harriet S.
Published: February 2005

▪ Abstract  The type IIa Na/phosphate (Pi) cotransporter (Npt2a) is expressed in the brush border membrane (BBM) of renal proximal tubular cells where the bulk of filtered Pi is reabsorbed. Disruption of the Npt2a gene in mice elicits hypophosphatemia, renal Pi wasting, and an 80% decrease in renal BBM Na/Pi cotransport, and led to the demonstration that Npt2a is the target for hormonal and dietary regulation of renal Pi reabsorption. Regulation is achieved by changes in BBM abundance of Npt2a protein and requires the interaction of Npt2a with various scaffolding and regulatory proteins. Molecular studies in patients with renal Pi wasting resulted in the identification of novel regulators of Pi homeostasis: fibroblast growth factor-23 (FGF-23) and a phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX). In mouse models, increased FGF-23 production or loss of Phex function causes hypophosphatemia and decreased renal Pi reabsorption, secondary to decreased BBM Npt2a protein abundance. Thus, Npt2a plays a major role in the maintenance of Pi homeostasis in both health and disease.
Identity Politics
Authors: Bernstein Mary
Published: February 2005

This review presents an overview of research on identity politics. First, I distinguish between various approaches to defining identity politics and the challenges presented by each approach. In the process, I show that these approaches reflect competing theoretical understandings of the relationship between experience, culture, identity, politics, and power. These debates raise theoretical issues that I address in the second section, including (a) how to understand the relationship between personal experience and political stance, (b) why status identities are understood and/or portrayed as essentialist or socially constructed, (c) the strategic dilemmas activists face when the identities around which a movement is organized are also the basis for oppression, (d) when to attribute certain movement outcomes to status identities, and (e) how to link collective action to specific notions of power to help explain the cultural and political goals at which identity politics is aimed. I conclude by recommending some promising avenues for future research.
Rapamycin inhibits fibronectin-induced migration of the human arterial smooth muscle line (E47) through the mammalian target of rapamycin
Authors: Sakakibara Kenji , Liu Bo , Hollenbeck Scott , Kent K. Craig
Published: February 2005

The matrix protein fibronectin (FN) is a potent agoinst of vascular smooth muscle cell (SMC) migration. The role of rapamycin and the mammalian target of rapamycin (mTOR) in matrix protein-induced migration has not yet been defined. In these studies, we found that rapamycin (10 nM) markedly diminished chemotaxis of E47 cells (a cell line derived from human atherosclerotic plaques) and rat aortic SMCs toward FN as well as type I collagen and laminin; however, a period of preincubation >20 h was required. Subsequently, we showed that treatment with FN induced a rapid activation of mTOR as well as its downstream effector, S6 kinase (S6K). Moreover, FN-induced activation of both proteins was inhibited by preincubation with rapamycin for only 30 min. We then explored the upstream signaling pathway through which FN might mediate mTOR activation. A blocking antibody to αvβ3inhibited FN-induced mTOR/S6K activation as well as E47 cell chemotaxis, implicating αvβ3as the integrin receptor responsible for initiating FN-induced migration. Moreover, preincubation of E47 cells with wortmannin or LY-294002 blocked FN-induced mTOR/S6K activation, demonstrating that phosphatidylinositol 3-kinase (PI3K) plays a critical role in this rapamycin-sensitive signaling pathway. It has been previously suggested that rapamycin's effect on migration maybe related to enhancement of p27kip1. However, treatment of E47 cells with rapamycin did not alter the level of p27kip1in the presence or absence of FN. Taken together, our data demonstrate that rapamycin inhibits FN-induced SMC migration through a pathway that involves at least αvβ3-integrin, PI3K, mTOR, and S6K.
RhoA and resistance artery remodeling
Authors: Loirand Gervaise , Rolli-Derkinderen Malvyne , Pacaud Pierre
Published: February 2005

Resistance arteries are able to adapt to physiological and pathophysiological stimuli to maintain adequate perfusion according to the metabolic demand of the tissue. Although vasomotor control allows rapid adaptation of lumen diameter, vascular remodeling constitutes an active process that occurs in response to long-term alterations of hemodynamic parameters. Unfortunately, this initially adaptive process contributes to the pathology of vascular diseases. Recent studies have demonstrated the participation of Rho protein signaling pathways in several cardiovascular pathologies including hypertension, coronary artery spasm, effort angina, atherosclerosis, and restenosis. Functional analyses have further revealed that RhoA-dependent pathways are involved in excessive contraction, migration, and proliferation associated with arterial diseases. The present review focuses on the role of Rho proteins, in particular RhoA, in vascular smooth muscle cells and the involvement of Rho-dependent signaling pathways in resistance artery remodeling, more particularly in relation to hypertension.
Ca2+-activated K+channel-associated phosphatase and kinase activities during development
Authors: Lin Mike T. , Longo Lawrence D. , Pearce William J. , Hessinger David A.
Published: February 2005

In ovine basilar arterial smooth muscle cells (SMCs), the fetal “big” Ca2+-activated K+(BK) channel activity is significantly greater and has a lower Ca2+setpoint than BK channels from adult cells. In the present study, we tested the hypothesis that these differences result from developmentally regulated phosphorylation of these channels. Using the patch-clamp technique and a novel in situ enzymological approach, we measured the rates and extents of changes in BK channel voltage activation from SMC inside-out patch preparations in response to selective activation and inhibition of channel-associated protein phosphatases and kinases (CAPAKs). We show that BK channel activity is modulated during development by differential phosphorylation and that the activities of CAPAKs change substantially during development. In particular, excised membrane patches from adult SMCs exhibited greater protein kinase A activity than those from a fetus. In contrast, fetal SMCs exhibited greater protein kinase G activity and phosphatase activity than adult SMCs. These findings extend our previous observation that the BK channel Ca2+setpoint differs significantly in adult and fetal cerebrovascular myocytes and suggest a biochemical mechanism for this difference. In addition, these findings suggest that the functional stoichiometry of CAPAKs varies significantly during development and that such variation may be a hitherto unrecognized mechanism of ion channel regulation.
Permissive contributions of NO and prostacyclin in CO-induced cerebrovascular dilation in piglets
Authors: Leffler Charles W. , Fedinec Alexander L. , Parfenova Helena , Jaggar Jonathan H.
Published: February 2005

Endogenously produced CO is an important dilator in newborn cerebrovascular circulation. CO dilates cerebral arterioles by activating Ca2+-activated K+channels, but modulatory actions of other effectors and second messenger inputs are unclear. Specifically, the mechanisms behind the obligatory permissive roles of prostacyclin and NO are uncertain. Therefore, the present study was performed using acutely implanted, closed cranial windows in newborn pigs to address the hypothesis that the permissive roles of NO and prostacyclin in cerebrovascular dilation in response to CO involve a common mechanism. The NO donor sodium nitroprusside restored dilation in response to CO after inhibition of that dilation with the prostaglandin cyclooxygenase inhibitor indomethacin. The stable prostacyclin analog iloprost restored CO-induced dilation blocked by the NO synthase inhibitor Nω-nitro-l-arginine. Restoration of dilation in response to CO by the cGMP-dependent phosphodiesterase inhibitor zaprinast and blockade of CO dilation by the guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazole-[4,3- a]quinoxalin-1-one (ODQ) suggests involvement of the cGMP/PKG pathway. Iloprost or the cAMP-dependent dilator isoproterenol restored dilation in response to CO after ODQ administration. However, CO-induced dilation blocked by the cGMP-dependent PKG inhibitor Rp-8-[(4-chlorophenyl)thio]-cGMPS triethylamine could not be reversed by administration of sodium nitroprusside, iloprost, or isoproterenol. Conversely, PKA inhibition did not block dilation in response to CO. Overall, data indicate that activation of PKG is the predominant mechanism of the permissive actions of NO and prostacyclin for CO-induced pial arteriolar dilation.
Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors
Authors: Hawkins Brian T. , Egleton Richard D. , Davis Thomas P.
Published: February 2005

Nicotine increases the permeability of the blood-brain barrier in vivo. This implies a possible role for nicotinic acetylcholine receptors in the regulation of cerebral microvascular permeability. Expression of nicotinic acetylcholine receptor subunits in cerebral microvessels was investigated with immunofluorescence microscopy. Positive immunoreactivity was found for receptor subunits α3, α5, α7, and β2, but not subunits α4, β3, or β4. Blood-brain barrier permeability was assessed via in situ brain perfusion with [14C]sucrose. Nicotine increased the rate of sucrose entry into the brain from 0.3 ± 0.1 to 1.1 ± 0.2 μl·g−1·min−1, as previously described. This nicotine-induced increase in blood-brain barrier permeability was significantly attenuated by both the blood-brain barrier-permeant nicotinic antagonist mecamylamine and the blood-brain barrier-impermeant nicotinic antagonist hexamethonium to 0.5 ± 0.2 and 0.3 ± 0.2 μl·g−1·min−1, respectively. These data suggest that nicotinic acetylcholine receptors expressed on the cerebral microvascular endothelium mediate nicotine-induced changes in blood-brain barrier permeability.
Differential binding of VEGF isoforms to VEGF receptor 2 in the presence of neuropilin-1: a computational model
Authors: Mac Gabhann Feilim , Popel Aleksander S.
Published: February 2005

A comprehensive, biophysically accurate, computational model of vascular endothelial growth factor (VEGF) family member interactions with endothelial cell surface receptors was developed to study angiogenesis. Neuropilin-1 (NRP1) and the signaling VEGF receptor, VEGFR2, do not interact directly but are bridged by one VEGF isoform, VEGF165. Using the model and published experimental data, we estimated the kinetic rate of this VEGFR2-NRP1 coupling in vitro. With the use of this rate, our model gives predictions in good quantitative agreement with several independent in vitro experiments involving VEGF121and VEGF165isoforms, confirming that VEGFR2-NRP1 coupling through VEGF165can fully explain the observed differences in receptor binding and phosphorylation in response to these isoforms. Model predictions also determine the mechanism of action of a commonly used NRP1 antibody and predict the results of potential future experiments. This is the first model to include VEGF isoforms or NRPs, and it is a necessary step toward a quantitative molecular level description of VEGF that can be extended to in vivo situations. The model has applications for both proangiogenic and antiangiogenic therapies, such as for heart disease and cancer, as well as in tissue engineering.
Age-related changes of bradykinin B1and B2receptors in rat heart
Authors: Kintsurashvili Ekaterina , Duka Arvi , Ignjacev Ivana , Pattakos Gregory , Gavras Irene , Gavras Haralambos
Published: February 2005

Aging is a major risk factor for the development of vascular diseases, such as hypertension and atherosclerosis, that leads to end organ damage and especially heart failure. Bradykinin has been demonstrated to have a cardioprotective role by affecting metabolic processes and tissue perfusion under conditions of myocardial ischemia. Its actions are exerted via the bradykinin B1- and B2-type receptors (B1Rs and B2Rs), but the functional status of these receptors during the aging process is poorly understood. This study aims to investigate whether changes in B1R and B2R gene and protein expression in rat heart are associated with the age-related alterations of cardiac structure and function. Using real-time PCR, we found that B1R mRNA expression increased 2.9-fold in hearts of older rats (24 mo of age) compared with younger rats (3 mo of age), whereas B2R gene expression remained unchanged. Western blot analysis showed that expression of B2R at the protein level is approximately twofold higher in young rats compared with old rats, whereas the B1R protein is approximately twofold higher in old rats compared with young rats. The present results provide clear functional and molecular evidence that indicate age-related changes of bradykinin B1Rs and B2Rs in heart. Because the cardioprotective actions of bradykinin are physiologically mediated via the B2Rs, whereas the B1Rs become induced by tissue damage, these results suggest that age-related decreases in B2R protein levels may leave the heart vulnerable to ischemic damage, and increases in B1R expression and activity may represent a compensatory reaction in aging hearts.
Intensive exercise training suppresses testosterone during bed rest
Authors: Wade C. E. , Stanford K. I. , Stein T. P. , Greenleaf J. E.
Published: February 2005

Spaceflight and prolonged bed rest (BR) alter plasma hormone levels inconsistently. This may be due, in part, to prescription of heavy exercise as a countermeasure for ameliorating the adverse effects of disuse. The initial project was to assess exercise programs to maintain aerobic performance and leg strength during BR. The present study evaluates the effect of BR and the performance of the prescribed exercise countermeasures on plasma steroid levels. In a 30-day BR study of male subjects, the efficacy of isotonic (ITE, n = 7) or isokinetic exercise (IKE, n = 7) training was evaluated in contrast to no exercise ( n = 5). These exercise countermeasures protected aerobic performance and leg strength successfully. BR alone (no-exercise group) did not change steroidogenesis, as assessed by the plasma concentrations of cortisol, progesterone, aldosterone, and free (FT) and total testosterone (TT). In the exercise groups, both FT and TT were decreased ( P < 0.05): FT during IKE from 24 ± 1.7 to 18 ± 2.0 pg/ml and during ITE from 21 ± 1.5 to 18 ± 1 pg/ml, and TT during IKE from 748 ± 68 to 534 ± 46 ng/dl and during ITE from 565 ± 36 to 496 ± 38 ng/dl. The effect of intensive exercise countermeasures on plasma testosterone was not associated with indexes of overtraining. The reduction in plasma testosterone associated with both the IKE and ITE countermeasures during BR supports our hypothesis that intensive exercise countermeasures may, in part, contribute to changes in plasma steroid concentrations during spaceflight.
Prenatal Screening for Thrombophilia: The Background and the Approach
Authors: James Andra H. , Brancazio Leo R.
Published: February 2005

Coagulation is a normal response to blood vessel injury and involves the interaction of endothelium, platelets and clotting factors. Coagulation is altered by pregnancy and may be further altered by thrombophilia, an acquired or inherited predisposition to develop thrombosis. An overview of coagulation is provided as background for understanding thrombophilia. Both acquired and genetic risk factors for thrombosis are discussed. Thrombosis may affect not only the maternal circulation, but the utero-placental-fetal circulation as well. The literature documenting the association between maternal thrombosis and thrombophilia is summarized, as is the recent data linking thrombophilia and poor pregnancy outcome. An approach to screening for thrombophilia is outlined and strategies for thromboprophylaxis are provided.
Use of Nandrolone Decanoate as an Adjuvant for Erythropoietin Dose Reduction in Treating Anemia in Patients on Hemodialysis
Authors: Sheashaa Hussein , Abdel-Razek Waleed , El-Husseini Amr , Selim Amal , Hassan Nabil , Abbas Tarek , El-Askalani Hassan , Sobh Mohamed
Published: February 2005

Background/Aims: Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. Methods: This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. Results: A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. Conclusion: Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients.
Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation
Authors: Morisada Tohru , Oike Yuichi , Yamada Yoshihiro , Urano Takashi , Akao Masaki , Kubota Yoshiaki , Maekawa Hiromitsu , Kimura Yoshishige , Ohmura Masako , Miyamoto Takeshi , Nozawa Shiro , Koh Gou Young , Alitalo Kari , Suda Toshio
Published: February 2005

Angiopoietin (Ang) signaling plays a role in angiogenesis and remodeling of blood vessels through the receptor tyrosine kinase Tie2, which is expressed on blood vessel endothelial cells (BECs). Recently it has been shown that Ang-2 is crucial for the formation of lymphatic vasculature and that defects in lymphangiogenesis seen in Ang-2 mutant mice are rescued by Ang-1. These findings suggest important roles for Ang signaling in the lymphatic vessel system; however, Ang function in lymphangiogenesis has not been characterized. In this study, we reveal that lymphatic vascular endothelial hyaluronan receptor 1-positive (LYVE-1+) lymphatic endothelial cells (LECs) express Tie2 in both embryonic and adult settings, indicating that Ang signaling occurs in lymphatic vessels. Therefore, we examined whether Ang-1 acts on in vivo lymphatic angiogenesis and in vitro growth of LECs. A chimeric form of Ang-1, cartilage oligomeric matrix protein (COMP)-Ang-1, promotes in vivo lymphatic angiogenesis in mouse cornea. Moreover, we found that COMP-Ang-1 stimulates in vitro colony formation of LECs. These Ang-1-induced in vivo and in vitro effects on LECs were suppressed by soluble Tie2-Fc fusion protein, which acts as an inhibitor by sequestering Ang-1. On the basis of these observations, we propose that Ang signaling regulates lymphatic vessel formation through Tie2. (Blood. 2005;105:4649-4656)
B-Raf–dependent expression of vascular endothelial growth factor–A in Kaposi sarcoma–associated herpesvirus-infected human B cells
Authors: Akula Shaw M. , Ford Patrick W. , Whitman Audy G. , Hamden Khalief E. , Bryan Benjaman A. , Cook Paul P. , McCubrey James A.
Published: February 2005

Kaposi sarcoma–associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) is etiologically linked to Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease. Vascular endothelial growth factor–A (VEGF-A) is one of the essential factors required in KSHV pathogenesis, mainly due to its ability to mediate angiogenesis. In this report we analyzed the relationship between Raf and VEGF-A expression in KSHV-infected hematopoietic cells. All of the KSHV-infected cell lines (derived from PEL) expressed higher levels of B-Raf and VEGF-A when compared with uninfected cells. Inhibition of Raf to mitogen-induced extracellular kinase (MEK) to extracellular signal-related kinase (ERK) signaling, either by the use of MEK inhibitor (PD98059) or by siRNA specific to B-Raf, significantly lowered VEGF-A expression. In addition, B-Raf–induced VEGF-A expression was demonstrated to be sufficient to enhance tubule formation in endothelial cells. Interestingly, we did not observe mutation in the B-Raf gene of the KSHV-infected PEL cell lines. Taken together, we report for the first time the ability of Raf-associated signaling to play a role in the expression of VEGF-A in KSHV-infected hematopoietic cells.
A statistical approach for array CGH data analysis
Authors: Picard Franck , Robin Stephane , Lavielle Marc , Vaisse Christian , Daudin Jean-Jacques
Published: February 2005

Background

Microarray-CGH experiments are used to detect and map chromosomal imbalances, by hybridizing targets of genomic DNA from a test and a reference sample to sequences immobilized on a slide. These probes are genomic DNA sequences (BACs) that are mapped on the genome. The signal has a spatial coherence that can be handled by specific statistical tools. Segmentation methods seem to be a natural framework for this purpose. A CGH profile can be viewed as a succession of segments that represent homogeneous regions in the genome whose BACs share the same relative copy number on average. We model a CGH profile by a random Gaussian process whose distribution parameters are affected by abrupt changes at unknown coordinates. Two major problems arise : to determine which parameters are affected by the abrupt changes (the mean and the variance, or the mean only), and the selection of the number of segments in the profile.

Results

We demonstrate that existing methods for estimating the number of segments are not well adapted in the case of array CGH data, and we propose an adaptive criterion that detects previously mapped chromosomal aberrations. The performances of this method are discussed based on simulations and publicly available data sets. Then we discuss the choice of modeling for array CGH data and show that the model with a homogeneous variance is adapted to this context.

Conclusions

Array CGH data analysis is an emerging field that needs appropriate statistical tools. Process segmentation and model selection provide a theoretical framework that allows precise biological interpretations. Adaptive methods for model selection give promising results concerning the estimation of the number of altered regions on the genome.
The responses of Ht22 cells to oxidative stress induced by buthionine sulfoximine (BSO)
Authors: Chen Jun , Small-Howard Andrea , Yin Amy , Berry Marla J
Published: February 2005

Background

glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells. It directly reacts with reactive oxygen species (ROS), functions as a cofactor of antioxidant enzymes, and maintains thiol redox potential in cells. GSH depletion has been implicated in the pathogenesis of neurological diseases, particularly to Parkinson's disease (PD). The purpose of this study was to investigate the change of cellular antioxidant status and basic cell functions in the relatively early stages of GSH depletion.

Results

in this study, GSH was depleted by inhibition of glutamylcysteine synthetase using buthionine sulfoximine (BSO) treatment in Ht22, a neuronal cell line derived from mouse hippocampus. Treatment with BSO produced dose-dependent decreases in total GSH level, Fe3+-reducing ability (FRAP assay), Cu2+-reducing ability (Antioxidant Potential, AOP assay), and ABTS free radical scavenging ability (ABTS assay) of the cells, but the sensitivity of these indicators to dosage varied considerably. Most of the changes were completed during the first 8 hours of treatment. Cell viability was tested by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) assay, and cells at lower density in culture were found to be more sensitive to GSH depletion. The activity of antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR), and copper/zinc superoxide dismutase (Cu/Zn-SOD) were affected by GSH depletion. A cDNA expression array assay of the effects of BSO treatment showed significantly decreased mRNA level for 3 genes, and significantly increased mRNA level for 10 genes, including the antioxidant enzymes Cu/Zn-SOD and thioredoxin peroxidase 2 (TPxII).

Conclusions

the study suggests that there are BSO-sensitive and BSO-resistant pools of GSH in Ht22 cells, and that different categories of antioxidant react differently to GSH depletion. Further, the effect of GSH status on cell viability is cell density dependent. Finally, the alterations in expression or activity of several antioxidant enzymes provide insight into the various cellular responses to GSH depletion.