bluuebunny/crossref_metadata_2025 huggingface dataset:
Caught in conspiracy: cooperation between DNA methylation and histone H3K9 methylation in the establishment and maintenance of heterochromatin
Authors: Stancheva Irina
Published: August 2005

Heritable patterns of gene expression and gene silencing are determined by chromatin states that either permit or restrict transcription. Restrictive heterochromatin in most eukaryotes is characterized by high levels of DNA methylation and histone H3 methylation at lysine 9. The functional relationship between these two modifications is the focus of intensive investigation in various organisms from fungi to mammals. Complex interactions have been discovered among various components of DNA methylation and histone methylation pathways, proteins involved in the formation of higher-order chromatin structure, chromatin remodelling activities, and RNA interference. This review discusses some aspects of this crosstalk and the cooperation between DNA methylation and histone H3K9 methylation in the establishment and maintenance of heterochromatin.Key words: DNA methylation, H3K9 methylation, heterochromatin.
Aerosol generation using a joint vapor–nuclei type generator: Factorial design to characterize its performance
Authors: Jeng Chwen-Jyh , Kindzierski Warren B , Smith Daniel W
Published: August 2005

The performance of a joint vapor–nuclei type aerosol generator was investigated using a 24 factorial design experiment. The generator produced stable, reproducible monodisperse aerosols with aerodynamic diameters from 0.79 to 3.1 µm. The geometric standard deviation (GSD) ranged from 1.09 to 1.31. The factorial design experiment indicated that atomizer flow rate and temperature of aerosol material were the significant factors that control the number mean diameter (NMD) of product aerosols, while the diameter of the condensation chimney had a significant effect on aerosol monodispersity. Among these significant factors, the generator had a rapid, reproducible response to atomizer flow rate. As a result, it was used as an adjustment parameter to fine-tune the performance of the generator. Its main effect on NMD was –1.3 µm per increase of 1.0 L/min in atomizer flow rate. Experimental results suggested that a power-law relationship could be used to predict the NMD of product aerosols. This study confirmed that the atomizer must produce >105 cm–3 of primary mists to generate monodisperse aerosols by heterogeneous condensation. Key words: aerosol generator, monodisperse, condensation, nuclei, factorial design, heterogeneous, homogeneous.
Interdisciplinary comparison of expert risk beliefs
Authors: Rizak Samantha , Hrudey Steve E
Published: August 2005

There is increasing awareness that discrepancies in risk judgments between experts, in addition to those with the public, are a major difficulty in achieving effective risk communication. A survey was conducted on members of different environmental disciplines to determine the extent to which they share similar beliefs and conceptual frameworks concerning several basic assumptions and concepts in environmental health risk assessment. Results indicate that divergent interpretations do exist among respondents on several issues. Although no sharp distinctions were found among the disciplines, differences of opinion were often apparent within each group indicating that even within a particular disciplinary field, members do not hold consistent views on these issues. In light of the apparent difficulties in evaluating and communicating risk, experts should evaluate their own knowledge and understanding of these concepts and should be fully aware of the strengths and limitations of the methods used for risk assessment. Key words: risk communication, risk judgement, environmental health risk assessment.
Waterborne disease: an old foe re-emerging?
Authors: Neumann Norman F , Smith Daniel W , Belosevic Miodrag
Published: August 2005

In developed countries, clean and safe drinking water is taken for granted, and water treatment processes used to mass-produce drinking water have been hailed as one of the top five engineering achievements of the 20th century. However, in the last decade, several waterborne disease outbreaks have made us painfully aware of the personal, economical, societal, and public health costs associated with the impact of waterborne disease. There is evidence to suggest that the prevalence of waterborne disease may be dramatically underestimated in developed countries and that routine endemic exposure to waterborne pathogens may occur more frequently than originally perceived. A variety of demographical, societal, environmental, and physiological emergence factors likely play critical roles in enhancing the frequency of transmission of pathogens to hosts. This review focuses on the scope and impact of waterborne disease in developed countries and identifies issues surrounding the potential for rapid global emergence or re-emergence of waterborne disease. We examine relevant literature on Cryptosporidium parvum and Escherichia coli O157 as model organisms of study that support these concepts. Key words: drinking water, treatment, public health, Cryptosporidium, Escherichia coli, emergence, pathogens, transmission, waterborne disease.
Effect of environmental characteristics onPythiumandMesocriconemaspp. in golf course greens in Alabama
Authors: Allen T W , Han D Y , Bowen K L
Published: August 2005

The role the environment has on populations of Pythium and Mesocriconema spp. was investigated at 5 golf course locations in east central Alabama. Every 4 to 5 weeks soil samples were collected from 3 golf greens on each of the 5 golf courses. Environmental data, including air and soil temperature, pH and relative humidity, were also collected. Dilution plating and a combined sieving and sugar flotation procedure were conducted to determine the populations of Pythium and Mesocriconema spp. for each month. Isolates of Pythium from 4 months were also identified. Pythium spp. populations increased as soil temperature and ambient air temperature prior to sampling decreased (P < 0.05). Pythium spp. populations were highest in the winter and lowest in the spring. At some locations, populations of Mesocriconema spp. increased as soil acidity and populations of Pythium spp. decreased (P < 0.05) and as ambient air temperature prior to sampling increased (P < 0.05). Eight species of Pythium were isolated from 4 months, with Pythium rostratum being the most commonly isolated. Results suggest that Pythium and Mesocriconema spp. prefer different soil environments.Key words: Cynodon dactylon × traansvalensis, Poa trivialis, ring nematodes, turfgrass.
Multiple non-ribosomal peptide synthetase genes determine peptaibol synthesis inTrichoderma virens
Authors: Wei Xianying , Yang Fuquan , Straney David C
Published: August 2005

Trichoderma virens, an imperfect fungus, is used as a biocontrol agent to suppress plant disease caused by soilborne fungal pathogens. Antimicrobial peptides it produces include peptaibols of 11, 14, and 18 amino acids in length. These peptaibols were previously reported to be synthesized by a non-ribosomal peptide synthetase (NRPS) encoded by the Tex1 gene in strain Tv29-8. The present study examined the Tex1 homolog in a commercially relevant T. virens strain, G20. Although the gene in G20 was 99% identical in DNA sequence to Tex1 in the 15.8 kb compared, gene disruption results indicate that it is only responsible for the production of an 18-mer peptaibol, and not 11-mer and 14-mer peptaibols. Additional NRPS adenylate domains were identified in T. virens and one was found to be part of a 5-module NRPS gene. Although the multimodule gene is not needed for peptaibol synthesis, sequence comparisons suggest that two of the individual adenylate domain clones might be part of a separate peptaibol synthesis NRPS gene. The results indicate a significant diversity of NRPS genes in T. virens that is unexpected from the literature.Key words: Hypocrea virens, Gliocladium virens, Trichoderma virens.
Diversity of organophosphorus pesticide-degrading bacteria in a polluted soil and conservation of their organophosphorus hydrolase genes
Authors: Zhang Ruifu , Cui Zhongli , Jiang Jiandong , He Jian , Gu Xiangyang , Li Shunpeng
Published: August 2005

Seven methyl parathion-degrading bacteria were isolated from a long-term methyl parathion contaminated soil and were found to belong to the genera Pseudaminobacter, Achromobacter, Brucella, and Ochrobactrum. Southern blot analysis using an mpd gene probe revealed that their hydrolase genes were similar to the mpd gene from Plesiomonas sp. strain M6 and were all located on the chromosome. Gene libraries were constructed from genomic DNA of each of the 7 organophosphorus pesticide-degrading bacteria, and their mpd genes were cloned and sequenced. Sequence analysis revealed that their hydrolase genes were conserved, and that the G+C content of the mpd genes were distinctly different from that of the chromosome-located 16S rRNA gene, suggesting that the mpd gene could be transferred and expressed among a variety of bacterial hosts.Key words: methyl parathion, degrading bacteria, Southern blot, mpd gene.
Cyclooxygenase inhibition with acetylsalicylic acid unmasks a role for prostacyclin in erythropoietin-induced hypertension in uremic rats
Authors: Rodrigue Marie-Ève , Lacasse-M Sonia , Larivière Richard , Lebel Marcel
Published: August 2005

We previously reported that thromboxane (TX)A2synthesis and receptor blockade prevented recombinant human erythropoietin (rhEPO)-induced hypertension in chronic renal failure rats. The present study was designed to investigate the effect of a cyclooxygenase inhibitor, acetylsalicylic acid (ASA), on blood pressure, renal function, and the concentration of eicosanoïds and endothelin-1 (ET-1) in vascular and renal tissues of rhEPO-treated or rhEPO-untreated uremic rats. Renal failure was induced by a 2-stage 5/6 renal mass ablation. Rats were divided into 4 groups: vehicle, rhEPO (100 U/kg, s.c., 3 times per week), ASA (100 mg·kg–1·day–1), and rhEPO + ASA; all animals were administered drugs for 3 weeks. The TXA2- and prostacyclin (PGI2)-stable metabolites (TXB2and 6-keto-PGF1α, respectively), as well as ET-1, were measured in renal cortex and either the thoracic aorta or mesenteric arterial bed. The uremic rats developed anemia, uremia, and hypertension. They also exhibited a significant increase in vascular and renal TXB2(p < 0.01) and 6-keto-PGF1α(p < 0.01) concentrations. rhEPO therapy corrected the anemia but aggravated hypertension (p < 0.05). TXB2and ET-1 tissue levels further increased (p < 0.05) whereas 6-keto-PGF1αwas unchanged in rhEPO-treated rats compared with uremic rats receiving the vehicle. ASA therapy did not prevent the increase in systolic blood pressure nor the progression of renal disease in rhEPO-treated or rhEPO-untreated uremic rats, but suppressed both TXB2and 6-keto-PGF1αtissue concentrations (p < 0.05). ASA had no effect on vascular and renal ET-1 levels. Cyclooxygenase inhibition had no effect on rhEPO-induced hypertension owing, in part, to simultaneous inhibition of both TXA2and its vasodilatory counterpart PGI2synthesis, whereas the vascular ET-1 overproduction was maintained. These results stress the importance of preserving PGI2production when treating rhEPO-induced hypertension under uremic conditions. Key words: hypertension, erythropoietin, renal failure, acetylsalicilic acid, prostacyclin, thromboxane, endothelin-1.
Reserpine-induced central effects: pharmacological evidence for the lack of central effects of reserpine methiodide
Authors: Nammi Srinivas , Boini Krishna Murthy , Koppula Sushruta , Sreemantula Satyanarayana
Published: August 2005

Reserpine, an alkaloid from Rauwolfia serpentina, was widely used for its antihypertensive action. However, its use has been reduced because of its sedative and extra pyramidal symptoms. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine, was synthesized and pharmacologically evaluated in rats and mice for its central (barbiturate hypnosis, spontaneous motor activity, body temperature, and avoidance of conditioned response) and peripheral actions (blood pressure) in comparison with reserpine. The results indicate that reserpine produced a dose-dependent depression of the central nervous system. RMI at doses equal to and double the equimolar doses of reserpine did not produce any behavioural changes compared with control animals. Nevertheless, both reserpine and RMI were found to produce dose-dependent reduction in the blood pressure of anaesthetized rats, although only at higher doses of RMI, indicating that quaternization of reserpine not only attenuated the entry of RMI into the central nervous system, but also reduced its access to the target tissue in the periphery. It is speculated that the hypotensive actions of RMI may also be due to peripheral depletion of catecholamines. Key words: resperine methiodide (RMI), reserpine, behaviour, blood pressure, mice, rats.
Causes of offspring mortality in the Antarctic fur seal, Arctocephalus gazella: the interaction of density dependence and ecosystem variability
Authors: Reid Keith , Forcada Jaume
Published: August 2005

Rates of pup production and causes of pup mortality, recorded in a designated study colony on Bird Island, South Georgia, from 1989 to 2003, were used to evaluate the factors influencing the growth of the population of Antarctic fur seals, Arctocephalus gazella (Peters, 1875). The mean number of pups produced per year was 680 (range 444–822) with a mean survival rate of 77.6% (range 52.6%–92.8%). Starvation, arising from reduced food availability within the mothers' foraging area, was the most frequently recorded cause of death and was positively correlated with the overall rate of pup survival, although it showed no relationship with the number of pups produced. However, traumatic injury showed a local relationship with seal density, increasing significantly with increasing numbers of seals born. This suggests that environmental processes that reduce the availability of prey to lactating mothers, rather than space limitation within colonies, are the limiting factor in the population increase of Antarctic fur seals at South Georgia. The spatial scales over which such processes operate, relative to the local-scale effects of densities of animals within colonies, have important implications for the future expansion of the population and the resultant trophodynamic interactions.
PION AND QUARK ANNIHILATION MECHANISMS OF DILEPTON PRODUCTION IN RELATIVISTIC HEAVY ION COLLISIONS
Authors: ANCHISHKIN D. , NARYSHKIN R.
Published: August 2005

The medium-induced modifications of the π+π- and [Formula: see text] annihilation mechanisms of dilepton production during relativistic heavy-ion collisions are considered in the frame of a specific model. The main assumption of the model: the pions (quarks) produced during a collision are effectively confined to a finite volume due to the dense hadron environment, in which they live for a finite time scaled as the lifetime of a fireball. The effect of the contraction of the phase space of the annihilating pion (quark) states on dilepton spectra is analyzed.
REVERSAL OF INTERFERENCE IN LEFT HANDED MEDIUM
Authors: MARIO LANDOBASA YOSEF , YUAN XIAOCONG , CHIN MEE-KOY
Published: August 2005

A material that has both negative permittivity and permeability is termed as left-handed material. The properties of Left Handed Material (LHM), such as negative refraction, have been simulated numerically by beam propagation method. The results are consistent with other works reported in the literature. It is shown that the Poynting vector and the phase velocity of the electromagnetic wave are indeed anti-parallel, confirming that the left-handed material does not violate the causality condition. It is conventional to simulate the phase restoring mechanism in a left-handed medium by showing (negative) refraction at an interface between an LHM and a conventional material. In this paper, we show for the first time, a simulation using BPM for the case of multiple-slit interference using Gaussian beam. The interference for two to three sources with different separations is used to show that the LHM can restore the phase and reverse the diffraction and interference effects.
HOST PLANT SELECTION BY APHIDS: Behavioral, Evolutionary, and Applied Perspectives
Authors: Powell Glen , Tosh Colin R. , Hardie Jim
Published: August 2005

▪ Abstract  As phloem feeders and major vectors of plant viruses, aphids are important pests of agricultural and horticultural crops worldwide. The processes of aphid settling and reproduction on plants therefore have a direct economic impact, and a better understanding of these events may lead to improved management strategies. Aphids are also important model organisms in the analysis of population differentiation and speciation in animals, and new ideas on plant utilization influence our understanding of the mechanisms generating biological diversity. Recent research suggests that the dominant cues controlling plant preference and initiation of reproduction are detected early during the stylet penetration process, well before the nutrient supply (phloem) is contacted. Aphids regularly puncture cells along the stylet pathway and ingest cytosolic samples, and the cues stimulating settling and parturition likely are metabolites present in peripheral (nonvascular) plant cells. We discuss these findings and their implications for aphid evolution and management.
Epithelial Cells and Their Neighbors. II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells
Authors: Flemström Gunnar , Sjöblom Markus
Published: August 2005

Surface sensory enteroendocrine cells are established mucosal taste cells that monitor luminal contents and provide an important link in transfer of information from gut epithelium to the central nervous system. Recent studies now show that these cells can also mediate efferent signaling from the brain to the gut. Centrally elicited stimulation of vagal and sympathetic pathways induces release of melatonin, which acts at MT2 receptors to increase mucosal electrolyte secretion. Psychological factors as well mucosal endocrine cell hyperplasia are implicated in functional intestinal disorders. Central nervous influence on the release of transmitters from gut endocrine cells offers an exciting area of future gastrointestinal research with a clinical relevance.
UT-A urea transporter promoter, UT-Aα, targets principal cells of the renal inner medullary collecting duct
Authors: Fenton Robert A. , Shodeinde Adetola , Knepper Mark A.
Published: August 2005

The urea transporters, UT-A1 and UT-A3, two members of the UT-A gene family, are localized to the terminal portion of the inner medullary collecting duct (IMCD). In this manuscript, we demonstrate that 4.2 kb of the 5′-flanking region of the UT-A gene (UT-Aα promoter) is sufficient to drive the IMCD-specific expression of a heterologous reporter gene, β-galactosidase (β-Gal), in transgenic mice. RT-PCR, immunoblotting, and immunohistochemistry demonstrate that within the kidney, transgene expression is confined to the terminal portion of the IMCD. Colocalization studies with aquaporin-2 show that expression is localized to the principal cells of the IMCD2 and IMCD3 regions. Utilizing β-Gal activity assays, we further show that within the kidney, the β-Gal transgene can be regulated by both water restriction and glucocorticoids, similar to the regulation of the endogenous UT-A gene. These results demonstrate that 4.2 kb of the UT-Aα promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific and cell-specific fashion in transgenic mice.
Prevalence of Dementia among Veterans Affairs Medical Care System Users
Authors: Krishnan Laura L. , Petersen Nancy J. , Snow A. Lynn , Cully Jeffrey A. , Schulz Paul E. , Graham David P. , Morgan Robert O. , Braun Ursula , Moffett Maurice L. , Yu Hong-Jen , Kunik Mark E.
Published: August 2005

Objectives: In an aging population, the number of veterans diagnosed with dementia is likely to increase. Knowledge of existing dementia prevalence will be beneficial in planning for future patient care needs. Our objectives were to assess the prevalence of the dementia diagnosis among those treated at Veterans Affairs (VA) medical centers and determine how it varies across race and Veterans Integrated Service Network (VISN). Materials and Methods: Data were collected on all veterans seen within the VA medical system from 1997 through the first half of 2001. Only veterans aged 65 and over were included in the study. Veterans were included if they had one of the following dementia ICD-9 codes: 290.XX, 291.2, 294.XX, 331.XX, 046.1, or 046.3. Results: The overall prevalence of dementia was 7.3%. The prevalence of dementia was similar among white patients and patients of other races, except African-American patients, in whom it was 50% higher. Across VISNs, the prevalence of dementia ranged from 5.8 to 9.4%. Alzheimer’s disease was the most frequently diagnosed type of dementia within the VA, and inpatient service utilization and outpatient psychiatry visits by individuals with dementia were high relative to other VA patients. Discussion: The overall prevalence identified is consistent with that reported in the literature, as is the elevated prevalence in African-Americans versus whites. The data on prevalence by VISN may identify regional variation in either the types of dementia present or the diagnostic criteria used. The dementia diagnosis is clearly associated with substantial service use.
High-Density Lipoprotein Deficiency and Dyslipoproteinemia Associated With Venous Thrombosis in Men
Authors: Deguchi Hiroshi , Pecheniuk Natalie M. , Elias Darlene J. , Averell Patricia M. , Griffin John H.
Published: August 2005

Background—

Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients.

Methods and Results—

We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoproteins AI and B in blood samples from 49 male venous thrombosis patients and matched controls aged <55 years. Venous thrombosis patients had significantly lower levels of HDL particles, large HDL particles, HDL cholesterol, and apolipoprotein AI and significantly higher levels of LDL particles and small LDL particles. The quartile-based odds ratios for decreased HDL particle and apolipoprotein AI levels in patients compared with controls were 6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl ester transfer protein were analyzed, patients differed significantly from controls in the allelic frequency for the
Taq
I B1/B2 polymorphism in cholesteryl ester transfer protein, consistent with the observed pattern of lower HDL and higher LDL.

Conclusions—

Venous thrombosis in men aged <55 years old is associated with dyslipoproteinemia involving lower levels of HDL particles, elevated levels of small LDL particles, and an elevated ratio of apolipoprotein B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related cholesteryl ester transfer protein genotype difference.
Toward a Political Rehabilitation of Environmentalism
Authors: Greear Jake P.
Published: August 2005

At present, the progress achieved by the environmental movements of the 20th century is being challenged or arrested on many fronts. Environmental legislation at the national level has encountered limits to its efficacy, liberalizing trends in global trade policies continue to undermine such legislation, and, particularly in the United States, publics have become increasingly hostile to many aspects of the environmentalist agenda. In his book Community and the Politics of Place, Daniel Kemmis provides a critical analysis of some limitations of contemporary American politics and focuses on the potential role of place in edifying more participatory forms of democratic practice. Kemmis’s book is becoming a foundational work in environmental thought because it speaks to the crises of contemporary environmentalism by presenting an alternative vision of political practice that has the potential to lead to more effective environmental policies while also mending the public image of environmentalism.
Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL)
Authors: Zambello Renato , Berno Tamara , Cannas Giovanna , Baesso Ilenia , Binotto Gianni , Bonoldi Emanuela , Bevilacqua Pierantonio , Miorin Marta , Facco Monica , Trentin Livio , Agostini Carlo , Semenzato Gianpietro
Published: August 2005

We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs. The topographic organization of GLs and DCs was also studied in bone marrow (BM) biopsies. Peripheral blood (PB) CD3- GLs from patients showed significant proliferative activity in the presence of iDCs and mDCs. Conversely, monoclonal CD3+ GLs were unresponsive to autologous and allogeneic PB DCs. Analysis of BM biopsies demonstrated a topographic distribution of DCs and GLs that indicates contact between the 2 cell types. On functional assays, DCs obtained from BM were more efficient than PB DCs in stimulating CD3- GLs, and surprisingly, a low but definite stimulatory effect was demonstrated also on CD3+ GLs. The putative contact between DCs and GLs in the BM and, more crucial, the proliferative response of discrete GL populations to DC stimulation suggest the presence of a specific antigen within BM DCs, providing evidence for a role of DCs in the pathogenesis of LDGL.
Cross genome phylogenetic analysis of human and Drosophila G protein-coupled receptors: application to functional annotation of orphan receptors
Authors: Metpally Raghu Prasad Rao , Sowdhamini Ramanathan
Published: August 2005

Background

The cell-membrane G-protein coupled receptors (GPCRs) are one of the largest known superfamilies and are the main focus of intense pharmaceutical research due to their key role in cell physiology and disease. A large number of putative GPCRs are 'orphans' with no identified natural ligands. The first step in understanding the function of orphan GPCRs is to identify their ligands. Phylogenetic clustering methods were used to elucidate the chemical nature of receptor ligands, which led to the identification of natural ligands for many orphan receptors. We have clustered human and Drosophila receptors with known ligands and orphans through cross genome phylogenetic analysis and hypothesized higher relationship of co-clustered members that would ease ligand identification, as related receptors share ligands with similar structure or class.

Results

Cross-genome phylogenetic analyses were performed to identify eight major groups of GPCRs dividing them into 32 clusters of 371 human and 113 Drosophila proteins (excluding olfactory, taste and gustatory receptors) and reveal unexpected levels of evolutionary conservation across human and Drosophila GPCRs. We also observe that members of human chemokine receptors, involved in immune response, and most of nucleotide-lipid receptors (except opsins) do not have counterparts in Drosophila. Similarly, a group of Drosophila GPCRs (methuselah receptors), associated in aging, is not present in humans.

Conclusion

Our analysis suggests ligand class association to 52 unknown Drosophila receptors and 95 unknown human GPCRs. A higher level of phylogenetic organization was revealed in which clusters with common domain architecture or cellular localization or ligand structure or chemistry or a shared function are evident across human and Drosophila genomes. Such analyses will prove valuable for identifying the natural ligands of Drosophila and human orphan receptors that can lead to a better understanding of physiological and pathological roles of these receptors.
β-adrenergic receptor activation in immortalized human urothelial cells stimulates inflammatory responses by PKA-independent mechanisms
Authors: Harmon Erin B , Porter Jill M , Porter James E
Published: August 2005

Background

Interstitial cystitis (IC) is a debilitating disease characterized by chronic inflammation of the urinary bladder, yet specific cellular mechanisms of inflammation in IC are largely unknown. Multiple lines of evidence suggest that β-adrenergic receptor (AR) signaling is increased in the inflamed urothelium, however the precise effects of these urothelial cell signals have not been studied. In order to better elucidate the AR signaling mechanisms of inflammation associated with IC, we have examined the effects of β-AR stimulation in an immortalized human urothelial cell line (UROtsa). For these studies, UROtsa cells were treated with effective concentrations of the selective β-AR agonist isoproterenol, in the absence or presence of selective inhibitors of protein kinase A (PKA). Cell lysates were analyzed by radioimmunoassay for generation of cAMP or by Western blotting for induction of protein products associated with inflammatory responses.

Results

Radioligand binding demonstrated the presence of β-ARs on human urothelial UROtsa cell membranes. Stimulating UROtsa cells with isoproterenol led to concentration-dependent increases of cAMP production that could be inhibited by pretreatment with a blocking concentration of the selective β-AR antagonist propranolol. In addition, isoproterenol activation of these same cells led to significant increases in the amount of phosphorylated extracellular signal-regulated kinase (pERK), inducible nitric oxide synthase (iNOS) and the induced form of cyclooxygenase (COX-2) when compared to control. Moreover, preincubation of UROtsa cells with the selective PKA inhibitors H-89 or Rp-cAMPs did not diminish this isoproterenol mediated phosphorylation of ERK or production of iNOS and COX-2.

Conclusion

Functional β-ARs expressed on human urothelial UROtsa cell membranes increase the generation of cAMP and production of protein products associated with inflammation when activated by the selective β-AR agonist isoproterenol. However, the increased production of iNOS and COX-2 by isoproterenol is not blocked when UROtsa cells are preincubated with inhibitors of PKA. Therefore, UROtsa cell β-AR activation significantly increases the amount of iNOS and COX-2 produced by a PKA-independent mechanism. Consequently, this immortalized human urothelial cell line can be useful in characterizing potential AR signaling mechanisms associated with chronic inflammatory diseases of the bladder.
Discharge and follow-up for people with stroke: what happens and why
Authors: Tyson Sarah , Turner Gill
Published: August 2005

Objective: To assess the quality of the process of discharge from hospital and follow-up services for people with stroke.

Design: A criterion-based process audit and basic outcome measures, combined with surveys of patients' satisfaction and staff opinion of the service.

Setting: All units treating stroke patients in a health care district including an acute and a community NHS trust, and 23 participating GP practices. Subjects: Process audit: documented notes of 98 stroke patients admitted and discharged over a four-month period. Patient satisfaction survey: 93 surviving stroke patients. Staff opinion survey: general practitioners, hospital doctors, therapists and nurses treating stroke patients throughout the district.

Results: A poor level of service was found. The main shortcomings were poor communication and liaison and a narrow focus of rehabilitation which concentrated on the assessment and provision of basic home care and activities of daily living (ADL) required to obtain discharge. There was a paucity of provision beyond this most basic level and little follow-up after discharge. Pass rates against agreed criteria were: communication between staff and patients/carers 47%, liaison between staff 44%, assessment of home-based needs 48%, assessment of domestic skills 15.5%. Fifty-one per cent of patients were referred for follow-up therapy and of these 72% started follow-up therapy within six weeks of discharge, only 27% had any follow-up assessment of activity levels and well-being. Patients were dissatisfied with the information, support services and therapy they received. The main reasons for the shortcomings were lack of awareness of the services provided, professionals' low expectations of patients' abilities, and limitations of community-based therapy services.

Conclusions: Evidence from other publications suggests that these results do not indicate a service that is any worse than other districts, rather it represents the poor deal offered to stroke patients. By comprehensively assessing several aspects of the service together this methodology has been able to reveal these inadequacies and the reasons for them.
Calcium Biology of the Transverse Tubules in Heart
Authors: SONG LONG‐SHENG , GUATIMOSIM SILVIA , GÓMEZ‐VIQUEZ LETICIA , SOBIE ERIC A. , ZIMAN ANDREW , HARTMANN HALI , LEDERER W. J.
Published: August 2005

Abstract: Ca2+ sparks in heart muscle are activated on depolarization by the influx of Ca2+ through dihydropyridine receptors in the sarcolemmal (SL) and transverse tubule (TT) membranes. The cardiac action potential is thus able to synchronize the [Ca2+]i transient as Ca2+ release is activated throughout the cell. Increases in the amount of Ca2+ within the sarcoplasmic reticulum (SR) underlie augmented Ca2+ release globally and an increase in the sensitivity of the ryanodine receptors (RyRs) to be triggered by the local [Ca2+]i. In a similar manner, phosphorylation of the RyRs by protein kinase A (PKA) increases the sensitivity of the RyRs to be activated by local [Ca2+]i. Heart failure and other cardiac diseases are associated with changes in SR Ca2+ content, phosphorylation state of the RyRs, [Ca2+]i signaling defects and arrhythmias. Additional changes in transverse tubules and nearby junctional SR may contribute to alterations in local Ca2+ signaling. Here we briefly discuss how TT organization can influence Ca2+ signaling and how changes in SR Ca2+ release triggering can influence excitation‐contraction (EC) coupling. High speed imaging methods are used in combination with single cell patch clamp experiments to investigate how abnormal Ca2+ signaling may be regulated in health and disease. Three issues are examined in this presentation: (1) normal Ca2+‐induced Ca2+ release and Ca2+ sparks, (2) abnormal SR Ca2+ release in disease, and (3) the triggering and propagation of waves of elevated [Ca2+]i.
Rhythmic Ca2+ Oscillations Drive Sinoatrial Nodal Cell Pacemaker Function to Make the Heart Tick
Authors: VINOGRADOVA TATIANA M. , MALTSEV VICTOR A. , BOGDANOV KONSTANTIN Y. , LYASHKOV ALEXEY E. , LAKATTA EDWARD G.
Published: August 2005

Abstract: Excitation‐induced Ca2+ cycling into and out of the cytosol via the sarcoplasmic reticulum (SR) Ca2+ pump, ryanodine receptor (RyR) and Na+‐Ca2+ exchanger (NCX) proteins, and modulation of this Ca2+cycling by β‐adrenergic receptor (β‐AR) stimulation, governs the strength of ventricular myocyte contraction and the cardiac contractile reserve. Recent evidence indicates that heart rate modulation and chronotropic reserve via β‐ARs also involve intracellular Ca2+ cycling by these very same molecules. Specifically, sinoatrial nodal pacemaker cells (SANC), even in the absence of surface membrane depolarization, generate localized rhythmic, submembrane Ca2+ oscillations via SR Ca2+ pumping‐RyR Ca2+ release. During spontaneous SANC beating, these rhythmic, spontaneous Ca2+ oscillations are interrupted by the occurrence of an action potential (AP), which activates L‐type Ca2+ channels to trigger SR Ca2+ release, unloading the SR Ca2+ content and inactivating RyRs. During the later part of the subsequent diastolic depolarization (DD), when Ca2+ pumped back into the SR sufficiently replenishes the SR Ca2+ content, and Ca2+‐dependent RyR inactivation wanes, the spontaneous release of Ca2+ via RyRs again begins to occur. The local increase in submembrane [Ca2+] generates an inward current via NCX, enhancing the DD slope, modulating the occurrence of the next AP, and thus the beating rate. β‐AR stimulation increases the submembrane Ca2+ oscillation amplitude and reduces the period (the time from the prior AP triggered SR Ca2+ release to the onset of the local Ca2+ release during the subsequent DD). This increased amplitude and phase shift causes the NCX current to occur at earlier times following a prior beat, promoting the earlier arrival of the next beat and thus an increase in the spontaneous firing rate. Ca2+ cycling via the SR Ca2+ pump, RyR and NCX, and its modulation by β‐AR stimulation is, therefore, a general mechanism of cardiac chronotropy and inotropy.
Cardiac Systems Biology
Authors: MCCULLOCH ANDREW D. , PATERNOSTRO GIOVANNI
Published: August 2005

Abstract: As more detailed molecular information accumulates on the biology of the heart and other complex systems in health and disease, the need for new integrative analyses and tools is growing. Systems biology and bioengineering seek to use high‐throughput technologies and integrative computational analysis to construct networks of the interactions between molecular components in the system, to develop systems models of their functionally integrated biological properties, and to incorporate these systems models into structurally integrated multi‐scale models for predicting clinical phenotypes. This review gives examples of recent applications using these approaches to elucidate the electromechanical function of the heart in aging and disease.
Modulation of Transmural Repolarization
Authors: ANTZELEVITCH CHARLES
Published: August 2005

Abstract: Ventricular myocardium in larger mammals has been shown to be comprised of three distinct cell types: epicardial, M, and endocardial. Epicardial and M cell action potentials differ from endocardial cells with respect to the morphology of phase 1. These cells possess a prominent Ito‐mediated notch responsible for the “spike and dome” morphology of the epicardial and M cell response. M cells are distinguished from the other cell types in that they display a smaller IKs, but a larger late INa and INa‐Ca. These ionic distinctions underlie the longer action potential duration (APD) and steeper APD‐rate relationship of the M cell. Difference in the time course of repolarization of phase 1 and phase 3 are responsible for the inscription of the electrocardiographic J wave and T wave, respectively. These repolarization gradients are sensitively modulated by electrotonic communication among the three cells types, [K1]o, and the presence of drugs that either reduce or augment net repolarizing current. A reduction in net repolarizing current generally leads to a preferential prolongation of the M cell action potential, responsible for a prolongation of the QT interval and an increase in transmural dispersion of repolarization (TDR), which underlies the development of torsade de pointes arrhythmias. An increase in net repolarizing current can lead to a preferential abbreviation of the action potential of epicardium in the right ventricle (RV), and endocardium in the left ventricle (LV). These actions also lead to a TDR that manifests as the Brugada syndrome in RV and the short QT syndrome in LV.
Extracellular Stimulation in Tissue Engineering
Authors: SELIKTAR DROR
Published: August 2005

Abstract: The field of tissue engineering has created a need for biomaterials that are capable of providing biofunctional and structural support for living cells outside of the body. Most of the commonly used biomaterials in tissue engineering are designed based on their physicochemical properties, thus achieving precise control over mechanical strength, compliance, porosity, and degradation kinetics. Biofunctional signals are added to the scaffold by tethering, immobilizing, or supplementing biofunctional macromolecules, such as growth factors, directly to the scaffold material. The challenge in tissue engineering remains to find the correct balance between the biofunctional and the physical properties of the scaffold material for each application. Moreover, the ability to modulate communication between cells and the extracellular environment using the engineered scaffold as the actuator can provide a significant advantage in tissue engineering. In this study, a unique scaffold material is presented. The material interchangeably combines biofunctional and structural molecules by fusing the two into a single backbone macromolecule. This integration provides the basis for practical, effective, and high‐resolution control of both the biofunctional and the physical properties of the scaffold material. This new scaffold material has proven effective with smooth muscle, cardiac, cartilage, and human embryonic stem cell cultures. The advantages of this approach as well as the potential applications of this unique scaffold material are discussed.
2,3,7,8-Tetrachlorodibenzo-p-Dioxin Increases Glycodelin Gene and Protein Expression in Human Endometrium
Authors: Mueller Michael D. , Vigne Jean-Louis , Streich Matthias , Tee Meng Kian , Raio Luigi , Dreher Ekkehard , Bersinger Nick A. , Taylor Robert N.
Published: August 2005

Context: Glycodelin (GdA) is an immunosuppressive endometrial glycoprotein critical for embryonic implantation and pregnancy establishment.

Objective: The aim of the present study was to examine the effect of dioxin [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] on GdA production in human endometrial cells.

Design: Controlled endometrial explant (EE) and cell cultures were used in this study.

Setting: Work was conducted at university hospital research laboratories in Bern, Switzerland, and in San Francisco, California.

Patients: Ovulatory women provided endometrial biopsies in the proliferative or secretory phase.

Intervention(s): EEs and cells were cultured without and with TCDD.

Main Outcome Measure(s): GdA protein and gene expression were quantified.

Results: A 2.5-fold increase in GdA production was demonstrated in EEs treated with 10 nm TCDD for 9 d. Fluorography revealed a 3- to 4-fold increase in new GdA biosynthesis and secretion in TCDD-treated endometrial epithelial cells. Because the action of dioxin is mediated by the aryl hydrocarbon receptor (AhR), we ascertained that primary epithelial and Ishikawa cells express AhR. Dose responses to TCDD and expressed AhR were established in transiently transfected Ishikawa cells using luciferase fusion vectors containing 1.0 kb of 5′ flanking DNA relative to the GdA transcriptional start site but not when shorter promoter constructs were used. A dioxin response element was mapped to nucleotides −539 to −533 of the gene promoter and verified by site-directed mutagenesis.

Conclusions: We demonstrated a direct AhR-mediated effect of dioxin on GdA gene transcription and protein secretion that might influence human female fertility.
Gene Expression Profiling of Orbital Adipose Tissue from Patients with Graves’ Ophthalmopathy: A Potential Role for Secreted Frizzled-Related Protein-1 in Orbital Adipogenesis
Authors: Kumar Seema , Leontovich Alexey , Coenen Michael J. , Bahn Rebecca S.
Published: August 2005

Context: The signs and symptoms of Graves’ ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles.

Objective: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO.

Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals.

Setting: The study took place at a private practice tertiary referral center.

Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease.

Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (>4-fold) in GO orbital tissues, whereas 11 genes were decreased (>4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-γ (44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nm) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures.

Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.
Increased Transvascular Lipoprotein Transport in Diabetes: Association with Albuminuria and Systolic Hypertension
Authors: Jensen Jan Skov , Feldt-Rasmussen Bo , Borch-Johnsen Knut , Jensen Kurt Svarre , Nordestgaard Børge Grønne
Published: August 2005

Context: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present.

Objective: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis.

Design: The study was cross-sectional and was performed in 1999–2002.

Setting: The study took place in the referral center.

Patients: The patients included 60 with diabetes mellitus (27 with type 1 diabetes and 33 with type 2 diabetes) and 42 healthy controls. All were randomly recruited.

Main Outcome Measure: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL). Autologous 131I-LDL was reinjected iv, and the 1-h fractional escape rate was taken as an index of transvascular transport.

Results: Transvascular LDL transport was 1.8 (1.6–2.0), 2.3 (2.0–2.6), and 2.6 (1.3–4.0)%/[h × (liter/m2)] in healthy controls, diabetic controls, and diabetes patients with systolic hypertension or albuminuria, respectively (P = 0.013; F = 4.5; df =2; ANOVA). These differences most likely were not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, or medicine use.

Conclusions: Transvascular LDL transport is increased in patients with diabetes mellitus, especially if systolic hypertension or albuminuria is present. Accordingly, lipoprotein flux into the arterial wall could be increased in these patients, possibly explaining accelerated development of atherosclerosis.