bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative Stress of
Burkholderia cenocepacia
Induces Insertion Sequence-Mediated Genomic Rearrangements That Interfere with Macrorestriction-Based Genotyping
Authors: Drevinek Pavel , Baldwin Adam , Lindenburg Laurens , Joshi Lovleen Tina , Marchbank Angela , Vosahlikova Sarka , Dowson Christopher G. , Mahenthiralingam Eshwar
Published: November 2009

Burkholderia cenocepacia
can cause serious infections and epidemics in patients with cystic fibrosis (CF). A CF population in the Czech Republic experienced an epidemic outbreak caused by a
B. cenocepacia
ST-32 strain. The clonality of the isolates was evident by multilocus sequence typing; however, fingerprinting profiles obtained by pulsed-field gel electrophoresis (PFGE) showed substantial band variability. We investigated whether the PFGE pattern diversity resulted from genomic rearrangements mediated by insertion sequences (IS); in addition, we determined whether stressful growth conditions altered the transposition activity of these IS. DNA probes for IS commonly found in
B. cenocepacia
were designed using the
B. cenocepacia
J2315 genome. Southern hybridization analysis of ST-32 isolates demonstrated diversity in both the copy number and the insertion site for a homologue of ISBcen20. Movement of the ISBcen20 homologue was detected when the ST-32 isolate CZ1238 was exposed to oxidative stress (growth in the presence of H
2
O
2
). PFGE analysis of CZ1238 derivatives exposed to oxidative stress demonstrated genomic rearrangements. Interestingly, when the closely related
B. cenocepacia
strain J2315 was exposed to oxidative stress, no movement of ISBcen20 was detected. Since frameshift mutations are present within the transposases of all copies of this IS in J2315, our data suggest that the transposase is inactive. In summary, we have demonstrated for the first time that IS movement can be mediated by oxidative stress and can lead to genomic rearrangements in the CF pathogen
B. cenocepacia
. These IS movements may alter the PFGE fingerprints of isolates that are clonal by other typing methods.
Corneal Graft Rejection Complicated by
Paracoccus yeei
Infection in a Patient Who Had Undergone a Penetrating Keratoplasty
Authors: Kanis M. J. , Oosterheert J. J. , Lin S. , Boel C. H. E. , Ekkelenkamp M. B.
Published: November 2009

A 68-year-old man who had undergone two penetrating keratoplasties of his left eye was admitted with early corneal graft failure. Culture of the anterior chamber fluid yielded
Paracoccus yeei
, a nonfermentative Gram-negative bacillus which thus far had only been implicated in ocular disease by means of PCR and 16S rRNA gene sequencing directly on patient material.
Blimp-1-Dependent Plasma Cell Differentiation Is Required for Efficient Maintenance of Murine Gammaherpesvirus Latency and Antiviral Antibody Responses
Authors: Siegel Andrea M. , Rangaswamy Udaya Shankari , Napier Ruth J. , Speck Samuel H.
Published: November 2009

Recent evidence from the study of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus supports a model in which terminal differentiation of B cells to plasma cells leads to virus reactivation. Here we address the role of Blimp-1, the master transcriptional regulator of plasma cell differentiation, in murine gammaherpesvirus 68 (MHV68) latency and reactivation. Blimp-1 expression in infected cells was dispensable for acute virus replication in the lung following intranasal inoculation and in the spleen following intraperitoneal inoculation with MHV68. However, we observed a role for Blimp-1 in both the establishment of latency and reactivation from latency
in vivo
. Additionally, plasma cell-deficient mice also exhibited a significant defect in the establishment of latency in the spleen, as well as reactivation from latency, similar to mice that lacked Blimp-1 only in MHV68-infected cells. In the absence of plasma cells, MHV68 infection failed to elicit a strong germinal center response and fewer B cells in the germinal center were MHV68 infected. Notably, the absence of a functional Blimp-1 gene only in MHV68-infected cells led to a decrease in both B-cell and CD4
+
T-cell responses during the establishment of latency. Finally, Blimp-1 expression in infected cells played a critical role in the maintenance of both MHV68 latency in the spleen and antibody responses to MHV68. Together, these studies support a model wherein episodic Blimp-1-mediated plasma cell differentiation leads to MHV68 reactivation, which serves to both renew the latency reservoirs and stimulate long-lived plasma cells to secrete virus-specific antibody.
Mouse-Specific Residues of Claudin-1 Limit Hepatitis C Virus Genotype 2a Infection in a Human Hepatocyte Cell Line
Authors: Haid Sibylle , Windisch Marc P. , Bartenschlager Ralf , Pietschmann Thomas
Published: November 2009

Recently, claudin-1 (CLDN1) was identified as a host protein essential for hepatitis C virus (HCV) infection. To evaluate CLDN1 function during virus entry, we searched for hepatocyte cell lines permissive for HCV RNA replication but with limiting endogenous CLDN1 expression, thus permitting receptor complementation assays. These criteria were met by the human hepatoblastoma cell line HuH6, which (i) displays low endogenous CLDN1 levels, (ii) efficiently replicates HCV RNA, and (iii) produces HCV particles with properties similar to those of particles generated in Huh-7.5 cells. Importantly, naïve cells are resistant to HCV genotype 2a infection unless CLDN1 is expressed. Interestingly, complementation of HCV entry by human, rat, or hamster CLDN1 was highly efficient, while mouse CLDN1 (mCLDN1) supported HCV genotype 2a infection with only moderate efficiency. These differences were observed irrespective of whether cells were infected with HCV pseudoparticles (HCVpp) or cell culture-derived HCV (HCVcc). Comparatively low entry function of mCLDN1 was observed in HuH6 but not 293T cells, suggesting that species-specific usage of CLDN1 is cell type dependent. Moreover, it was linked to three mouse-specific residues in the second extracellular loop (L152, I155) and the fourth transmembrane helix (V180) of the protein. These determinants could modulate the exposure or affinity of a putative viral binding site on CLDN1 or prevent optimal interaction of CLDN1 with other human cofactors, thus precluding highly efficient infection. HuH6 cells represent a valuable model for analysis of the complete HCV replication cycle in vitro and in particular for analysis of CLDN1 function in HCV cell entry.
Protective Memory Responses Are Modulated by Priming Events prior to Challenge
Authors: Rutigliano John A. , Morris Melissa Y. , Yue Wen , Keating Rachael , Webby Richard J. , Thomas Paul G. , Doherty Peter C.
Published: November 2009

Human infections with highly pathogenic H5N1 avian influenza A viruses in the last decade have legitimized fears of a long-predicted pandemic. We thus investigated the response to secondary infections with an engineered, but still highly virulent, H5N1 influenza A virus in the C57BL/6 mouse model. Mice primed with the H1N1 A/Puerto Rico/8/34 (PR8) virus were partially protected from lethality following respiratory infection with the modified H5N1 virus A/Vietnam/1203/04 (ΔVn1203). In contrast, those that had been comparably exposed to the HKx31 (H3N2) virus succumbed to the ΔVn1203 challenge, despite similarities in viral replication, weight loss, and secondary CD8+-T-cell response characteristics. All three viruses share the internal genes of PR8 that are known to stimulate protective CD8+-T-cell-mediated immunity. This differential survival of PR8- and HKx31-primed mice was also apparent for antibody-deficient mice challenged with the ΔVn1203 virus. The relative protection afforded by PR8 priming was abrogated in tumor necrosis factor-deficient (TNF−/−) mice, although lung fluids from the B6 HKx31-primed mice contained more TNF early after challenge. These data demonstrate that the nature of the primary infection can influence pathological outcomes following virulent influenza virus challenge, although the effect is not clearly correlated with classical measures of CD8+-T-cell-mediated immunity.
Upregulation of STAT3 Marks Burkitt Lymphoma Cells Refractory to Epstein-Barr Virus Lytic Cycle Induction by HDAC Inhibitors
Authors: Daigle Derek , Megyola Cynthia , El-Guindy Ayman , Gradoville Lyn , Tuck David , Miller George , Bhaduri-McIntosh Sumita
Published: November 2009

A fundamental problem in studying the latent-to-lytic switch of Epstein-Barr virus (EBV) and the viral lytic cycle itself is the lack of a culture system fully permissive to lytic cycle induction. Strategies to target EBV-positive tumors by inducing the viral lytic cycle with chemical agents are hindered by inefficient responses to stimuli. In vitro, even in the most susceptible cell lines, more than 50% of cells latently infected with EBV are refractory to induction of the lytic cycle. The mechanisms underlying the refractory state are not understood. We separated lytic from refractory Burkitt lymphoma-derived HH514-16 cells after treatment with an HDAC inhibitor, sodium butyrate. Both refractory- and lytic-cell populations responded to the inducing stimulus by hyperacetylation of histone H3. However, analysis of host cell gene expression showed that specific cellular transcripts Stat3, Fos, and interleukin-8 (IL-8) were preferentially upregulated in the refractory-cell population, while IL-6 was upregulated in the lytic population. STAT3 protein levels were also substantially increased in refractory cells relative to untreated or lytic cells. This increase in de novo expression resulted primarily in unphosphorylated STAT3. Examination of single cells revealed that high levels of STAT3 were strongly associated with the refractory state. The refractory state is manifest in a unique subpopulation of cells that exhibits different cellular responses than do lytic cells exposed to the same stimulus. Identifying characteristics of cells refractory to lytic induction relative to cells that undergo lytic activation will be an important step in developing a better understanding of the regulation of the EBV latent to lytic switch.
The metabolic syndrome: common origins of a multifactorial disorder
Authors: Bruce K D , Byrne C D
Published: November 2009

The metabolic syndrome (MetS) represents a combination of cardiometabolic risk determinants including obesity (central adiposity), insulin resistance, glucose intolerance, dyslipidaemia, non-alcoholic fatty liver disease and hypertension. MetS is rapidly increasing in prevalence worldwide as a consequence of the continued obesity “epidemic”, and as a result will have a considerable impact on the global incidence of cardiovascular disease and type 2 diabetes. Currently, there is debate concerning whether the risk of cardiovascular disease is greater in patients diagnosed with MetS than that of the sum of the individual risk factors. At present, no unifying origin that can explain the pathogenesis of MetS has been identified and therefore no unique pharmacological treatment is available. This review summarises and critically evaluates the current clinical and scientific evidence supporting the existence of MetS as a multifactorial endocrine disease, for which maternal nutrition may be a common pathogenic mechanism. In addition, we suggest that ectopic fat accumulation (such as visceral and hepatic fat accumulation) and the proinflammatory state are central to the development of the MetS.
Factors that influence decisions about cardiopulmonary resuscitation: the views of doctors and medical students
Authors: Tyrer F , Williams M , Feathers L , Faull C , Baker I
Published: November 2009

Background

A number of studies have explored doctors’ views and experiences of cardiopulmonary resuscitation (CPR), but to our knowledge there has been no research to identify the information that doctors take into account when they make decisions about CPR.

Purpose of study

To investigate factors that influence decisions about CPR.

Study design

Qualitative study involving six focus groups with 17 doctors and four medical students in Leicester, UK.

Results

Doctors and medical students considered a number of factors important when making decisions about CPR—namely, the patient’s diagnosis, prognosis, age, quality of life, the opinions of doctors and other medical staff, and the wishes of patients and relevant others. The relative importance of each of these factors varied significantly and was influenced by the doctors’ own beliefs and values.

Conclusions

Doctors would benefit from greater support for their decision making in relation to resuscitation to reduce variability in clinical practice and to promote appropriate patient care. Identification of factors that influence doctors’ individual beliefs, attitudes and values towards resuscitation and improvement in the quality of patient communication may help to guide policy in this area.
The histological basis of leaf dimorphism in Selaginella martensii
Authors: Dengler Nancy G.
Published: November 2009

The dorsiventral shoot system of Selaginella martensii is characterized by opposite pairs of dorsal and ventral leaves that are dimorphic in size and form. Some of the anatomical features associated with this dimorphism are related to the orientation of the shoot with regard to light, e.g., the abaxial epidermis of the small dorsal leaves and the adaxial epidermis of the large ventral leaves consist of conical cells of approximately the same size containing a single cup-shaped plastid. The shaded epidermal layers (abaxial in ventral and adaxial in dorsal leaves) consist of tabular cells with numerous small plastids; measurement of cell area in these layers shows a significant difference between leaf types. Other features of leaf anatomy do not show that same relationship to the direction of light: stomata are found on the morphologically abaxial side of the leaf regardless of orientation, as are the epidermal sclereids. The mesophyll is homogeneous and lacks a palisade layer. These quantitative observations extend earlier descriptions and provide a basis for future studies of development of these dimorphic leaf types.
Root rot of irrigated lentils in Iran
Authors: Kaiser Walter J. , Horner Glenn M.
Published: November 2009

In some areas of Iran, root rot of irrigated lentils (Lens culinaris) was a serious problem resulting in high plant mortality and decreased yields. Pythium ultimum was the predominant soil-borne pathogen isolated from discolored, necrotic roots of diseased plants in furrow-irrigated fields at Karaj, and appeared to be the primary incitant of root rot of irrigated lentils at several other locations in the country. Pythium aphanidermatum was the primary pathogen isolated from roots of diseased lentils at two irrigated sites in southern Iran. Isolates of P. ultimum and P. aphanidermatum were highly pathogenic on roots of lentil in greenhouse inoculation studies. Other fungi isolated from diseased lentil roots less frequently were Rhizoctonia solani, Phytophthora sp., Macrophomina phaseolina, Fusarium oxysporum, F. roseum, and F. solani. Cultures of R. solani, Phytophthora sp., and M. phaseolina were less pathogenic on lentil roots than either Pythium sp., whereas the three Fusarium spp. were nonpathogens. Incidence and severity of root rot increased in Karaj field trials in treatments receiving N and P fertilizer and irrigation every 6 days. In greenhouse tests, incidence of root rot increased when naturally infested Karaj soils were amended with 1 or 10% cow manure before planting. Sources of resistance to the lentil root rot complex were found in germplasm screened in naturally infested soils at Karaj.
Preliminary evidence for the involvement of suberization in infection of Casuarina
Authors: Berg R. Howard
Published: November 2009

Histochemistry of infected cells in mature nodule lobes of Casuarina showed that walls of infected host cells had a ligninlike component (ultraviolet-stimulated autofluorescence and staining with auramine O, phloroglucinol staining, and resistance to degradation by hydrolytic enzymes). Cytoplasm of infected cells had a pronounced affinity for lipid stains (Sudan black B, Rose Bengal fluorescence), though walls of infected cells were less clearly stained. When nodules were digested several days in cold 50% chromic acid, the walls of infected cells and suberized host tissue (epidermis, endodermis) were not degraded. Endophyte cell wall components were also found to be resistant to chromic acid digestion. The digested tissue retained the capacity to adsorb lipid dyes. These observations suggested that walls of infected host cells had become impregnated with a suberinlike compound. The hydrophobic quality of this wall was evident when its ultrastructure was examined after en bloc staining with the polar stain KMnO4. This stain did not penetrate the walls of mature infected cells, perhaps because of the presence of aliphatic compounds similar to those found in suberin. As is known for suberizing tissue, peroxidase activity (via diaminobenzidine oxidation) was high in nodule cortical tissue cell walls. The peroxidase stain was also localized on endophyte hyphae. This report is the first instance associating a suberizationlike host reaction with infection of an actinorhizal plant.
A light microscope study of resistant and susceptible carnations infected with Fusarium oxysporum f.sp. dianthi
Authors: Harling R. , Taylor G. S.
Published: November 2009

An anatomical study of infection by Fusarium oxysporum Schlecht. f.sp. dianthi (Prill, et Del.) Snyd. and Hans, in the stems of a resistant carnation (Dianthus caryophyllus L.) cultivar, and a susceptible cultivar, was carried out to determine host structural responses to infection which might be important in resistance to the fungus. Histological examination of stems at 2–24 days following inoculation revealed certain features of infection which were common to both the resistant and the susceptible cultivars. These were colonization of the xylem vessels and surrounding tissues, hyperplasia, hypertrophy and altered cytoplasmic activity of the xylem parenchyma, blockage of vessels with gels, and swelling of the vessel pit membranes between pit pairs. Gel formation was associated with paratracheal parenchyma cells. However, the extent and timing of some of these features were different between the two cultivars. The susceptible cultivar showed extensive colonization and destruction of xylem vessels and surrounding tissues, limited hyperplasia, and limited vascular gelation which was also slow to occur. In contrast, the resistant cultivar had less colonization and destruction of xylem, extensive areas of hyperplastic xylem parenchyma which sometimes surrounded groups of infected vessels, and rapid and extensive gelation of the xylem vessels in advance of fungal colonization. The rapid gelation response, together with the hyperplasia, were considered to be responsible for the physical containment of the fungus in the resistant cultivar and are therefore an important part of the defence mechanism in this host against the pathogen.
CORRELATION ENERGIES CALCULATIONS FOR POLY (p-PHENYLENEVINYLENE) (PPV) CHAINS
Authors: ZHAO HUA
Published: November 2009

The present study calculates correlation energies of the different length poly(p-phenylenevinylene) (PPV) units using the formula recently developed for π conjugated polymers, and analyzes the correlation energies from the phenylene unit and the vinylene unit in single and three PPV unit cells as well as the effect of the correlation energies on the band energy gap of the PPV. The present method avoids the complicated numerical computations about the correlation effects for the π electronic conjugated molecule systems with large unit cells.
Sildenafil inhibits chronically hypoxic upregulation of canonical transient receptor potential expression in rat pulmonary arterial smooth muscle
Authors: Lu Wenju , Ran Pixin , Zhang Dandan , Peng Gongyong , Li Bing , Zhong Nanshan , Wang Jian
Published: November 2009

In pulmonary arterial smooth muscle cells (PASMCs), Ca2+influx through store-operated Ca2+channels thought to be composed of canonical transient receptor potential (TRPC) proteins is an important determinant of intracellular free calcium concentration ([Ca2+]i) and pulmonary vascular tone. Sildenafil, a type V phosphodiesterase inhibitor that increases cellular cGMP, is recently identified as a promising agent for treatment of pulmonary hypertension. We previously demonstrated that chronic hypoxia elevated basal [Ca2+]iin PASMCs due in large part to enhanced store-operated Ca2+entry (SOCE); moreover, ex vivo exposure to prolonged hypoxia (4% O2for 60 h) upregulated TRPC1 and TRPC6 expression in PASMCs. We examined the effect of sildenafil on basal [Ca2+]i, SOCE, and the expression of TRPC in PASMCs under prolonged hypoxia exposure. We also examined the effect of sildenafil on TRPC1 and TRPC6 expression in pulmonary arterial smooth muscle (PA) from rats that developed chronically hypoxic pulmonary hypertension (CHPH). Compared with vehicle control, treatment with sildenafil (300 nM) inhibited prolonged hypoxia induced increases of 1) basal [Ca2+]i, 2) SOCE, and 3) mRNA and protein expression of TRPC in PASMCs. Moreover, sildenafil (50 mg · kg−1· day−1) inhibited mRNA and protein expression of TRPC1 and TRPC6 in PA from chronically hypoxic (10% O2for 21 days) rats, which was associated with decreased right ventricular pressure and right ventricular hypertrophy. Furthermore, we found, in PASMCs exposed to prolonged hypoxia, that knockdown of TRPC1 or TRPC6 by their specific small interference RNA attenuated the hypoxic increases of SOCE and basal [Ca2+]i, suggesting a cause and effect link between increases of TRPC1 and TRPC6 expression and the hypoxic increases of SOCE and basal [Ca2+]i. These results suggest that sildenafil may alter basal [Ca2+]iin PASMCs by decreasing SOCE through downregulation of TRPC1 and TRPC6 expression, thereby contributing to decreased vascular tone of pulmonary arteries during the development of CHPH.
Relationship between gene expression of duodenal iron transporters and iron stores in hemochromatosis subjects
Authors: Nelson James E. , Mugford Virginia R. , Kilcourse Ellen , Wang Richard S. , Kowdley Kris V.
Published: November 2009

To test the hypothesis that differences in duodenal iron absorption may explain the variable phenotypic expression among HFE C282Y homozygotes, we have compared relative gene expression of duodenal iron transporters among C282Y homozygotes [hereditary hemochromatosis (HH)] with and without iron overload. Duodenal biopsy samples were analyzed using real-time PCR for expression of DMT1, FPN1, DCYTB, and HEPH relative to GAPDH from 23 C282Y homozygotes, including 5 “nonexpressors” (serum ferritin < upper limit of normal and absence of phenotypic features of hemochromatosis) and 18 “expressors.” Four subjects of wild type for HFE mutations without iron overload or liver disease served as controls. There was a significant difference in expression of DMT1 ( P = 0.03) and DMT1(IRE) ( P = 0.0013) but not FPN1, DCYTB, or HEPH between groups. Expression of DMT1(IRE) was increased among HH subjects after phlebotomy compared with untreated ( P = 0.006) and nonexpressor groups ( P = 0.026). A positive relationship was observed among all HH subjects regardless of phenotype or treatment status between relative expression of FPN1 and DMT1 ( r = 0.5854, P = 0.0021), FPN1, and DCYTB ( r = 0.5554, P = 0.0040), FPN1 and HEPH ( r = 0.5100, P = 0.0092), and DCYTB and HEPH ( r = 0.5400, P = 0.0053). In summary, phlebotomy is associated with upregulation of DMT1(IRE) expression in HH subjects. HFE C282Y homozygotes without phenotypic expression do not have significantly decreased duodenal gene expression of iron transport genes compared with HH subjects with iron overload. There is coordinated regulation between duodenal expression of FPN1 and DMT1, FPN1 and DCYTB, and FPN1 and HEPH and also DCYTB and HEPH in HH subjects regardless of phenotype.
Comparison of two models of intrauterine growth restriction for early catch-up growth and later development of glucose intolerance and obesity in rats
Authors: Shahkhalili Yasaman , Moulin Julie , Zbinden Irene , Aprikian Olivier , Macé Katherine
Published: November 2009

Two models of intrauterine growth restriction, maternal food restriction (FR), and dexamethasone (DEX) exposure were compared for early postnatal catch-up growth and later development of glucose intolerance and obesity in Sprague-Dawley rats. Mated dams were randomly divided into three groups at 10 days gestational age. Group FR was food restricted (50% of nongestating rats) during the last 11 days of gestation; Group DEX received DEX injections during the last week of gestation, and Group CON, the control group, had no intervention. Birth weight, catch-up growth, body weight, and food intake were measured in male offspring for 22 wk. Body composition, blood glucose, and plasma insulin in response to a glucose load were assessed at 8, 16, and 22 wk. Pups from both FR and DEX dams had similarly lower birth weights than CON (22% and 25%, P < 0.0001), but catch-up growth, which occurred during the suckling period, was much more rapid in FR than DEX offspring (6 vs. 25 days, 95% CI). Postweaning, there were no significant differences between groups in food intake, body weight, body fat, and plasma insulin, but baseline plasma glucose at 22 wk and 2-h glucose area-under-the-curve at 8 and 22 wk were greater only in FR vs. CON offspring ( P < 0.05), thereby contrasting with the lack of significant differences between DEX and CON. These results suggest that prenatal food restriction is a more sensitive model than DEX exposure for studies aimed at investigating the link between low birth weight, early postnatal catch-up growth, and later development of glucose intolerance.
Pulsatile gonadotropin-releasing hormone release from hypothalamic explants of male marmoset monkeys compared with male rats
Authors: Woller Michael J. , Tannenbaum Pam L. , Schultz-Darken Nancy J. , Eshelman Bruce D. , Abbott David H.
Published: November 2009

The present study was conducted to quantify in vitro gonadotropin-releasing hormone (GnRH) release parameters in the male marmoset. We established primary cultures of marmoset hypothalamic tissues for ∼2 days (marmosets) to assess GnRH release profiles in vitro in hypothalamic explants from testis-intact and gonadectomized males. Pulsatile GnRH release profiles were readily demonstrated from in vitro hypothalamic explants isolated from adult male marmoset monkeys. Gonadectomy of male marmosets resulted in elevated mean GnRH and pulse amplitude from hypothalamic explants on the 1st day of culture ( day 0). GnRH pulse amplitude increased by day 2 in ∼67% of hypothalamic explants from testis-intact marmosets, suggesting release from an endogenous regulator of GnRH. We also measured GnRH release profiles in vitro in hypothalamic explants from testis-intact and gonadectomized rats. Male rats showed no changes in any concentration or frequency release parameters for GnRH following gonadectomy or during successive days in culture. The present study represents a unique examination of GnRH release from male marmoset monkey hypothalamic tissue and compares release dynamics directly with those obtained from male rat, suggesting a species difference in feedback regulation of GnRH release.
Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism
Authors: Olson Kenneth R. , Whitfield Nathan L. , Bearden Shawn E. , St. Leger Judy , Nilson Erika , Gao Yan , Madden Jane A.
Published: November 2009

Hypoxic pulmonary vasoconstriction (HVC), an intrinsic and assumed ubiquitous response of mammalian pulmonary blood vessels, matches regional ventilation to perfusion via an unknown O2-sensing mechanism. Global pulmonary hypoxia experienced by individuals suffering from chronic obstructive pulmonary disease or numerous hypoventilation syndromes, including sleep apnea, often produces maladaptive pulmonary hypertension, but pulmonary hypertension is not observed in diving mammals, where profound hypoxia is routine. Here we examined the response of cow and sea lion pulmonary arteries (PA) to hypoxia and observed the expected HVC in the former and a unique hypoxic vasodilation in resistance vessels in the latter. We then used this disparate response to examine the O2-sensing mechanism. In both animals, exogenous H2S mimicked the vasoactive effects of hypoxia in isolated PA. H2S-synthesizing enzymes, cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfur transferase, were identified in lung tissue from both animals by one-dimensional Western blot analysis and immunohistochemistry. The relationship between H2S production/consumption and O2was examined in real time by use of amperometric H2S and O2sensors. H2S was produced by sea lion and cow lung homogenate in the absence of O2, but it was rapidly consumed when O2was present. Furthermore, consumption of exogenous H2S by cow lung homogenate, PA smooth muscle cells, and heart mitochondria was O2dependent and exhibited maximal sensitivity at physiologically relevant Po2levels. These studies show that HVC is not an intrinsic property of PA and provide further evidence for O2-dependent H2S metabolism in O2sensing.
Hierarchical Bayesian Modeling and Markov Chain Monte Carlo Sampling for Tuning-Curve Analysis
Authors: Cronin Beau , Stevenson Ian H. , Sur Mriganka , Körding Konrad P.
Published: November 2009

A central theme of systems neuroscience is to characterize the tuning of neural responses to sensory stimuli or the production of movement. Statistically, we often want to estimate the parameters of the tuning curve, such as preferred direction, as well as the associated degree of uncertainty, characterized by error bars. Here we present a new sampling-based, Bayesian method that allows the estimation of tuning-curve parameters, the estimation of error bars, and hypothesis testing. This method also provides a useful way of visualizing which tuning curves are compatible with the recorded data. We demonstrate the utility of this approach using recordings of orientation and direction tuning in primary visual cortex, direction of motion tuning in primary motor cortex, and simulated data.
Chemopreventive Efficacy of Naproxen and Nitric Oxide–naproxen in Rodent Models of Colon, Urinary Bladder, and Mammary Cancers
Authors: Steele Vernon E. , Rao Chinthalapally V. , Zhang Yuting , Patlolla Jagan , Boring Daniel , Kopelovich Levy , Juliana M. Margaret , Grubbs Clinton J. , Lubet Ronald A.
Published: November 2009

Nonsteroidal anti-inflammatory drugs (NSAID) have been highly effective in preventing colon, urinary bladder, and skin cancer preclinically, and also in clinical trials of colon adenoma formation. However, certain NSAIDs cause gastrointestinal ulceration and may increase cardiovascular events. Naproxen seems to cause the lowest cardiovascular events of the common NSAIDs other than aspirin. Nitric oxide (NO)-naproxen was tested based on the finding that adding a NO group to NSAIDs may help alleviate GI toxicity. In the azoxymethane-induced rat colon aberrant crypt foci (ACF) model, naproxen administered at 200 and 400 ppm in the diet reduced mean ACFs in the colon by about 45% to 60%, respectively. NO-naproxen was likewise administered in the diet at roughly equimolar doses (300 and 600 ppm) and reduced total ACF by 20% to 40%, respectively. In the hydroxybutyl (butyl) nitrosamine rat urinary bladder cancer model, NO-naproxen was given at 183 or 550 ppm in the diet, and naproxen at 128 ppm. The NO-naproxen groups had 77% and 73% decreases, respectively, in the development of large urinary bladder tumors, whereas the 128 ppm naproxen group also showed a strong decrease (69%). If treatments were started 3 months after hydroxybutyl (butyl) nitrosamine, NO-naproxen (550 ppm) and naproxen (400 ppm) were also highly effective (86-94% decreases). In the methylnitrosourea-induced mammary cancer model in rats, NO-naproxen and naproxen showed nonsignificant inhibitions (12% and 24%) at 550 and 400 ppm, respectively. These data show that both naproxen and NO-naproxen are effective agents against urinary bladder and colon, but not mammary, carcinogenesis.
Oral Cancer Prevention Advances with a Translational Trial of Green Tea
Authors: Shin Dong M.
Published: November 2009

This perspective on Tsao et al. (beginning on p. 931 in this issue of the journal) discusses green tea extract, which was shown for the first time to have dose-dependent effects in a clinical chemopreventive setting (oral premalignant lesions). This translational trial provides important data on angiogenesis and other biomarkers on which to base future clinical research, which should include trials of green tea extract or polyphenols combined with other natural or synthetic compounds to enhance chemopreventive effects.
An Extended and Improved Special Sensor Microwave Imager (SSM/I) Period of Record
Authors: Semunegus Hilawe , Berg Wesley , Bates John J. , Knapp Kenneth R. , Kummerow Christian
Published: November 2009

The National Oceanic and Atmospheric Administration National Climatic Data Center has served as the archive of the Defense Meteorological Satellite Program Special Sensor Microwave Imager (SSM/I) data from the F-8, F-10, F-11, F-13, F-14, and F-15 platforms covering the period from July 1987 to the present. Passive microwave satellite measurements from SSM/I have been used to generate climate products in support of national and international programs. The SSM/I temperature data record (TDR) and sensor data record (SDR) datasets have been reprocessed and stored as network Common Data Form (netCDF) 3-hourly files. In addition to reformatting the data, a normalized anomaly (z score) for each footprint temperature value was calculated by subtracting each radiance value with the corresponding monthly 1° grid climatological mean and dividing it by the associated climatological standard deviation. Threshold checks were also used to detect radiance, temporal, and geolocation values that were outside the expected ranges. The application of z scores and threshold parameters in the form of embedded quality flags has improved the fidelity of the SSM/I TDR/SDR period of record for climatological applications. This effort has helped to preserve and increase the data maturity level of the longest satellite passive microwave period of record while completing a key first step before developing a homogenized and intercalibrated SSM/I climate data record in the near future.
Extracting Meaningful Information from Uncalibrated Backscattered Echo Intensity Data
Authors: Gostiaux Louis , van Haren Hans
Published: November 2009

The authors present an original method for the analysis of acoustic Doppler current profiler (ADCP) echo intensity profiles measured in the ocean, especially when no calibration has been performed. This study is based on data from Teledyne RD Instrument acoustic profilers but provides a methodology that can be extended to other kinds of hardware. To correctly interpret data for which the signal-to-noise ratio is below a factor of 10, the authors propose isolating the backscattered signal from noise in arithmetic space before resolving the sonar equation and compensating for transmission loss in logarithmic space. The robustness of the method is shown for several independent datasets from the Atlantic Ocean, the North Sea, and the Mediterranean Sea. Estimation of sediment concentration, planktonic migrations, or air bubbles is now possible at less than 10 dB above noise level, which can concern half of the ADCP’s range under common circumstances.
The Shift of Environmental Debates in Russia
Authors: Yanitsky Oleg N.
Published: November 2009

This article presents the results of long-term research aimed at identifying the major trends in environmental debates conditioned by Russian reforms and by the changing geopolitical situation of the Russian nation-state. The main topics of the article are changes in the very subject of these debates, the actors involved, the political opportunity structure of the debates and the character of the languages used by their participants. Four major shifts have been identified and analysed: first, from long-term to short-term issues; second, from nationwide to ‘insular’ debates conditioned by the division of Russians into those who live in time and in space; third, from value-centred to economically oriented; and fourth, from humanistic to social-technological. Epistemologically, these shifts indicate a process of transition from instructive to discursive production of scientific knowledge that should take into account local knowledge; in terms of sociology of social knowledge, this means a change in the relationships between science and publics that have acquired a right to speak; in cultural terms, it marks a shift from scientific to cultural rationality; and in institutional and organizational terms, it means a shift from debates in big national public arenas to issue-centred bargaining in which official and citizen experts compete.
The Author and Authorship in the Internet Society
Authors: Longo Mariano , Magnolo Stefano
Published: November 2009

The Internet is the most recent and relevant innovation in the field of media communication, as well as the medium that reproduces most of the characteristics of global society. In trying to describe contemporary society, we cannot neglect the social implication of the web. Our assumption is that the evolution of the Internet has led to problematic effects on the relevance of concepts such as individuality, author, authorship and copyright, as commonly used up till now. The first part of the article focuses on individuality as a means to describe individual actors and social structures in the first modernity, paying particular attention to the idea of the author as an individual in the field of intellectual products. New communication forms online make the connection between the individuality of the author and the text weaker and less recognizable. The second part develops the theme of scientific knowledge in contemporary society, with regard to scholarly authorship. The Internet has produced deep transformations in scholarly publications. Technical and structural characteristics of the Internet suggest possibilities for a reorganization of the scientific system towards the replacement of authorship and reputation with innovative mechanisms of information processing and selection.
The Oath of Office as Public Value Guardian
Authors: Rutgers Mark R.
Published: November 2009

The oath of office is perhaps the ultimate means to set public office apart: Public functionaries in most countries have to swear to let public interests prevail over private concerns. This seems at odds with the prevailing liberal/managerial idea that public and private employment is not distinct at all. The oath of office establishes a moral commitment to the office that transcends a contractual, managerial, and/or legal approach to public authority. It signifies the guardianship of public officers and links personal conscience with public values and public interests. This article concludes that we should guard against using an oath of office as a remedy against increased reliance on private interests and motivations; rather the latter may endanger a public service ethics and annul any meaning and function an oath may still represent to begin with.
A New Multicultural Population
Authors: Brown Monica R.
Published: November 2009

Multiracial families make up the fastest growing demographic in the United States. Approximately 9% of the U.S. population is multiracial, and it is estimated that the numbers will climb to 21% by 2050. With this increasing population, educators have a new responsibility to meet the needs of these families. Education must begin to form partnerships with families to increase the social and academic achievement of children from multiracial backgrounds. The purpose of this article is to (a) identify the uniqueness of multiracial students and families, (b) provide recommendations regarding improving multiracial family partnerships, and (c) offer best practices and strategies for working effectively with multiracial children and youth in schools.
Collective Action and Adaptive Socioecological Cycles in Premodern States
Authors: Blanton Richard
Published: November 2009

Resiliency theorists propose that ecological transformations result when ecosystems collapse and then are reorganized through a process they call adaptive cycles. This article investigates the degree to which the dynamic properties of adaptive cycles reflect, in part, the influence of political factors associated with collective action in state formation. The author evaluates this possibility using historical and archaeological data coded as part of a comparative study of 30 premodern states. From these data, the author investigates the socionatural consequences of various regime-building strategies, and the author concludes that collective action political process will be an important factor to consider in future studies of socioecological resilience and transformation.
Psychosocial characteristics of drunk drivers assessed by the Addiction Severity Index, prediction of relapse
Authors: Hubicka Beata , Laurell Hans , Bergman Hans
Published: November 2009

Aims: To investigate psychosocial characteristics and problems of a representative sample of Swedish drunk drivers with special consideration of the gender of the driver; analyze criminal records of the drivers before and after enrolment in the study; identify psychosocial predictors of relapse to drunk driving. Methods: Psychosocial characteristics were assessed by the Addiction Severity Index (ASI). Alcohol problems were additionally assessed by the Alcohol Use Disorders Identification Test (AUDIT). Criminal records were collected for the five year period before the enrolment, and for the subsequent two years, from Sweden’s official crime statistics. Results: About half of the investigated drivers had other psychosocial problems besides the drink driving offence. Female drivers had more alcohol, drug, psychiatric and relational problems, including with parents when growing up, than male drivers, but less previous and subsequent criminality. Heavily drunk drivers (blood alcohol concentration ≥0.1%) had more problems with alcohol, legal status and employment and support than the other drunk drivers. Problems with legal status, family and social relations and alcohol use increased the risk of relapse in drunk driving, while medical problems seemed to be a protective factor. Different ASI risk factors were identified for relapse in either traffic offences or other crimes. Conclusions: As well as the drunk driving offence, drunk drivers often have other psychosocial problems, female drivers in particular. Already the blood alcohol concentration per se gives some indication of the psychosocial problem profile of a drunk driver and the ASI profile has some prognostic value for relapse in drunk driving.
Recognizing the enhancement of graduate attributes and employability through part-time work while at university
Authors: Muldoon Robyn
Published: November 2009

The encouragement of the development of a set of graduate attributes to enhance employability in universities is not new. Mostly, however, it takes place within the formal curriculum. This article presents a case study of the outcomes of an institutional award for student development through extra-curricular activity. There are three categories of extra-curricular activity which qualify for the award: non-accredited learning and training; professional development; and community/voluntary work. The professional development category includes part-time work. This article focuses on just one component of the institutional award: part-time work. It looks at the range of paid and voluntary work undertaken by students during their studies, what they gain from it in terms of graduate attributes and the impact of institutional recognition of it. It seems that part-time work is a useful avenue for the development of graduate attributes and other desirable personal qualities, and enhances students’ employability. Additionally, students appear to benefit from institutional recognition of extra-curricular achievement while at university. Because of the small sample size, the results of this study may not be generalizable but the underlying notion of recognizing and rewarding student development through part-time work is transferable.
Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy
Authors: Samarasinghe Sujith , Mancao Christoph , Pule Martin , Nawroly Niga , Karlsson Helen , Brewin Jennifer , Openshaw Peter , Gaspar H. Bobby , Veys Paul , Amrolia Persis J.
Published: November 2009

Immunotherapy with allodepleted donor T cells (ADTs) improves immunity after T cell–depleted stem cell transplantation, but infection/relapse remain problematic. To refine this approach, we characterized the expression of surface markers/cytokines on proliferating alloreactive T cells (ATs). CD25 was expressed on 83% of carboxyfluorescein diacetate succinimidyl esterdim ATs, confirming this as an excellent target for allodepletion. Seventy percent of CD25− ATs expressed CD71 (transferrin receptor), identifying this as a novel marker to target ATs persisting after CD25 depletion. Comparison of residual alloreactivity after combined CD25/71 versus CD25 immunomagnetic depletion showed enhanced depletion of alloreactivity to host with CD25/71 depletion in both secondary (2°) mixed lymphocyte reactions (P < .01) and interferon-γ enzyme-linked immunospot assays (P < .05) with no effect on third-party responses. In pentamer/interferon-γ enzyme-linked immunospot assays, antiviral responses to cytomegalovirus, Epstein-Barr virus, and adenovirus were preserved after CD25/71 allodepletion. CD25/71 ADTs can be redirected to recognize leukemic targets through lentiviral transfer of a chimeric anti-CD19ζ T-cell receptor. Finally, we have established conditions for clinically applicable CD25/71 allodepletion under European Union Good Manufacturing Practice conditions, resulting in highly effective, reproducible, and selective depletion of ATs (median residual alloreactivity to host in 2° mixed lymphocyte reaction of 0.39% vs third-party response of 62%, n = 5). This strategy enables further clinical studies of adoptive immunotherapy with larger doses of ADTs to enhance immune reconstitution after T cell-depleted stem cell transplantation.
Dysregulation of bone remodeling by imatinib mesylate
Authors: Vandyke Kate , Fitter Stephen , Dewar Andrea L. , Hughes Timothy P. , Zannettino Andrew C. W.
Published: November 2009

Imatinib mesylate is a rationally designed tyrosine kinase inhibitor that has revolutionized the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Although the efficacy and tolerability of imatinib are a vast improvement over conventional chemotherapies, the drug exhibits off-target effects. An unanticipated side effect of imatinib therapy is hypophosphatemia and hypocalcemia, which in part has been attributed to drug-mediated changes to renal and gastrointestinal handling of phosphate and calcium. However, emerging data suggest that imatinib also targets cells of the skeleton, stimulating the retention and sequestration of calcium and phosphate to bone, leading to decreased circulating levels of these minerals. The aim of this review is to highlight our current understanding of the mechanisms surrounding the effects of imatinib on the skeleton. In particular, it examines recent studies suggesting that imatinib has direct effects on bone-resorbing osteoclasts and bone-forming osteoblasts through inhibition of c-fms, c-kit, carbonic anhydrase II, and the platelet-derived growth factor receptor. The potential application of imatinib in the treatment of cancer-induced osteolysis will also be discussed.