bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic diguanylate turnover mediated by the sole GGDEF/EAL response regulator in Pseudomonas putida: its role in the rhizosphere and an analysis of its target processes
Authors: Matilla Miguel A. , Travieso María L. , Ramos Juan L. , Ramos‐González María Isabel
Published: May 2011

GGDEF and EAL/HD‐GYP protein domains are responsible for the synthesis and hydrolysis of the bacterial secondary messenger cyclic diguanylate (c‐di‐GMP) through their diguanylate cyclase and phosphodiesterase activities, respectively. Forty‐three genes in Pseudomonas putida KT2440 are putatively involved in the turnover of c‐di‐GMP. Of them only rup4959 (locus PP4959) encodes a GGDEF/EAL response regulator, which was identified in a genome wide analysis as preferentially induced while this bacterium colonizes roots and adjacent soil areas (the rhizosphere). By using fusions to reporter genes it was confirmed that the rup4959 promoter is active in the rhizosphere and inducible by corn plant root exudates and microaerobiosis. Transcription of rup4959 was strictly dependent on the alternative transcriptional factor σS. The inactivation of the rup4959‐4957 operon altered the expression of 22 genes in the rhizosphere and had a negative effect upon oligopeptide utilization and biofilm formation. In multicopy or when overexpressed, rup4959 enhanced adhesin LapA‐dependent biofilm formation, the development of wrinkly colony morphology, and increased Calcofluor stainable exopolysaccharides (EPS). Under these conditions the inhibition of swarming motility was total and plant root tip colonization considerably less efficient, whereas swimming was partially diminished. This pleiotropic phenotype, which correlated with an increase in the global level of c‐di‐GMP, was not acquired with increased levels of Rup4959 catalytic mutant at GGDEF as a proof of this response regulator exhibiting diguanylate cyclase activity. A screen for mutants in putative targets of c‐di‐GMP led to the identification of a surface polysaccharide specific to KT2440, which is encoded by the genes cluster PP3133‐PP3141, as essential for phenotypes associated with increased c‐di‐GMP. Cellulose and alginate were discarded as the overproduced EPS, and lipopolysaccharide (LPS) core and O‐antigen were found to be essential for the development of wrinkly colony morphology.
Histochemical, immunohistochemical, and ultrastructural observations of the esophagus morphology of Rinella icterica (Anuran, Bufonidae)
Authors: Pelli‐Martins Adriana A. , Machado‐Santos Clarice , Sales Armando , de Brito‐Gitirana Lycia
Published: May 2011

Pelli‐Martins, A.A., Machado‐Santos, C., Sales, A. and de Brito‐Gitirana, L. 2011. Histochemical, immunohistochemical, and ultrastructural observations of the esophagus morphology of Rinella icterica (Anuran, Bufonidae). —Acta Zoologica (Stockholm) 93: 373–380.

The esophagus of Rinella icterica was analyzed by employing histochemical methods and lectin histochemistry at light microscopy as well as by transmission electron microscopy. The mucosa was composed of a ciliated columnar pseudostratified epithelium with goblet cells, overlying a lamina propria. The goblet cells contained neutral and acid glycoconjugates and were positive for galactose residues. Moreover, two types of goblet cells were identified; one type was positive for mannose, and the other was negative. Serotonin‐immunoreactive cells (5HT‐IR) occurred randomly scattered at the base of the epithelium; they were also localized between the mucous cells of the gland. Both submucosa and adventitia were composed of loose connective tissue, and the muscularis was formed by smooth muscle. Although the basic morphology of the esophagus of R. icterica is similar to that of mammals, the esophagus showed some morphological differences that are likely to be related to the specific physiology of the tissue.
Mineral density and bone remodelling markers in patients with calcium lithiasis
Authors: Arrabal‐Polo Miguel Angel , Arrabal‐Martin Miguel , de Haro‐Munoz Tomas , Lopez‐Leon Victor M. , Merino‐Salas Sergio , Ochoa‐Hortal Miguel Angel , Garrido‐Gomez Juan , Lahoz‐Garcia Clara , Zuluaga‐Gomez Armando
Published: May 2011

Study Type – Aetiology (case control)

Level of Evidence 3b

What’s known on the subject? and What does the study add?

Hypercalciuria is related with bone mineral density loss.

This study demonstrates the relationship between recurrent calcium nephrolithiasis and bone mineral density loss and their correlation with bone markers.

OBJECTIVES

• To show that a relationship exists between the loss of bone mineral density (BMD) and calcium renal lithiasis and that bone remodelling markers correlate with changes in BMD.

• It is possible that many cases hypercalciuria are related to the increase of bone turnover and the predominance of bone resorption phenomena.

PATIENTS AND METHODS

• The present study comprised a transversal investigation in three groups: group O, without lithiasis; group A, with a single episode of lithiasis; and group B, with relapsed calcium renal lithiasis.

• An analysis was made of body mass index; abdominal X‐ray and/or urography and renal ultrasonography; osteocalcin and β‐crosslaps bone markers; calcium and citrate concentrations in the urine; and femur and spinal column bone densitometry.

• The results were analyzed by analysis of variance and Pearson’s correlation coefficient.

RESULTS

• Patients with relapsed calcium renal lithiasis present a greater BMD loss than those in the O or A groups.

• Densitometry: T‐score femur −0.2 group O, −0.5 group A, −1.2 group B (P= 0.001); T‐score column −0.6 group O, −0.6 group A, −1.3 group B (P= 0.05).

• A statistically significant negative correlation exists between values of β‐crosslaps and T‐score femur (R=−0.251; P= 0.009) and T‐score column (R=−0.324; P= 0.001); thus, a higher concentration of β‐crosslaps was accompanied by a lower value of the T‐score and a greater loss of BMD.

• A positive relationship is observed between β‐crosslaps and osteocalcin (R= 0.611; P < 0.001) and between calciuria and cocient β‐crosslaps/osteocalcin (R= 0.303; P= 0.001).

CONCLUSIONS

• A statistically significant relationship is shown between the loss of BMD and relapsed calcium renal lithiasis.

• Determination of bone remodelling markers (i.e. osteocalcin and β‐crosslaps) facilitates the diagnosis of osteopaenia/osteoporosis in these patients.
Metastatic potential of a renal mass according to original tumour size at presentation
Authors: Umbreit Eric C. , Shimko Mark S. , Childs M. Adam , Lohse Christine M. , Cheville John C. , Leibovich Bradley C. , Blute Michael L. , Thompson R. Houston
Published: May 2011

Study Type – Prognosis (case series)

Level of Evidence 4

OBJECTIVE • To determine the metastatic potential of renal masses based on original tumour size.

MATERIALS AND METHODS • We identified 2651 patients who had undergone surgical resection for a unilateral, sporadic renal tumour between 1990 and 2006.

• Associations of tumour size with synchronous metastasis at presentation [M1 renal cell carcinoma (RCC)] and development of metastases, death from RCC, and death from any cause after surgery were evaluated using logistic and Cox proportional hazards regression.

RESULTS • Of the 2651 patients studied, 182 (6.9%) presented with M1 RCC. Tumour size was significantly greater in patients with M1 RCC than in patients with M0 RCC (a median size of 10 vs 4.5 cm; P < 0.001). Only 1 of the 629 patients (0.2%) with a tumour <3 cm had M1 RCC and that tumour was 2.5 cm. The risk of M1 RCC increased from 1.1% for patients with tumours 3–3.9 cm to 16.5% for patients with tumours ≥7 cm.

• Of the 2124 patients with M0 RCC, 430 developed distant metastases at a median (range) of 1.4 (0.1–16.2) years after surgery. Only 9 of the 498 patients (1.8%) with a tumour <3 cm developed distant metastases after surgery.

• Each 1‐cm increase in tumour size increased the risk of death from RCC by 20%[hazard ratio (HR) 1.20; 95% confidence interval (CI) 1.18–1.22; P < 0.001] and death from any cause by 10% (HR 1.10; 95% CI 1.09–1.12; P < 0.001).

• For the 1346 patients who were still alive at last follow‐up, the median (range) duration of follow‐up was 6.9 (0.1–19.7) years.

CONCLUSIONS • Tumour size is significantly associated with metastases in patients with renal masses.

• Patients with tumours <3 cm have a low risk of synchronous metastatic disease.
EQUILIBRIA EXISTENCE AND CHARACTERIZATION IN AUCTIONS: ACHIEVEMENTS AND OPEN QUESTIONS
Authors: de Castro Luciano I. , Karney Daniel H.
Published: May 2011

Abstract Establishing existence and characterizing equilibria are both important achievements in the study of auctions. However, we recognize that equilibria existence results form the basis for well accepted characterizations. In this survey, we review the landmark results and highlight open questions regarding equilibria existence and characterizations in auctions. In addition, we review the standard assumptions underlying these results, and discuss the suitability of the Nash equilibrium solution concept. We focus our review on single‐object auctions, but also review results in multi‐unit, divisible, combinatorial and double auctions.
On the Product of Inverse Wishart and Normal Distributions with Applications to Discriminant Analysis and Portfolio Theory
Authors: BODNAR TARAS , OKHRIN YAREMA
Published: May 2011

Abstract.  In this article we analyse the product of the inverse Wishart matrix and a normal vector. We derive the explicit joint distribution of the components of the product. Furthermore, we suggest several exact tests of general linear hypothesis about the elements of the product. We illustrate the developed techniques on examples from discriminant analysis and from portfolio theory.
Transparency and Manipulation of Public Accounts
Authors: GAVAZZA ALESSANDRO , LIZZERI ALESSANDRO
Published: May 2011

We study the policy choices of an incumbent politician when voters imperfectly observe aggregate spending and the incumbent’s ability. We show that total spending is decreasing in the transparency of spending, but increasing in the transparency of the incumbent’s ability. The model further provides a possible explanation of the choice of inefficient tools of redistribution, and investigates the incentives for politicians to manipulate public accounts. We show that politicians may choose inefficient and manipulable tools, but that this choice has positive welfare consequences because it leads to a reduction in spending.
From the Shadow Price of Capital to the Marginal Cost of Funds: In Search of the Implementation of a Principle
Authors: LIU LIQUN
Published: May 2011

The “folk principle” for multi‐period project evaluation states that if all the costs and benefits of a project are expressed as withdrawals from and increments to private consumption at different time points, then the appropriate discount rate is the consumer's rate of interest. The shadow price of capital (SPC) approach intends to implement this principle, but faces serious practical difficulties. By taking a utility‐based perspective, this paper explains why the SPC approach cannot fully implement the folk principle even theoretically. Then, it derives, as a complete implementation of the folk principle, a multi‐period cost‐benefit rule that is based on the concept of the marginal cost of funds.
Power of Incentives with Motivated Agents in Public Organizations
Authors: NAEGELEN FLORENCE , MOUGEOT MICHEL
Published: May 2011

Public service motivation is often considered as an argument for low‐powered incentive schemes in the public sector. In this paper, we characterize the optimal contract between a public regulator and an altruistic agent according to the degree α of public service motivation, when the type of the public service consumer is privately observed. We show that the requested effort is nondecreasing with α and can be higher than the first‐best level. Moreover, we show that the agent is put on a high‐powered contract when some customers are served but that this contract is associated with different types of consumers according to α. In contrast, the agent is never put on a cost‐plus contract. Finally, we show that the first‐best allocation can be achieved under budget balance for a degree of altruism higher than a threshold that we characterize.
A Dynamic Model of Public Opinion Formation
Authors: FATAS‐VILLAFRANCA FRANCISCO , SAURA DULCE , VAZQUEZ FRANCISCO J.
Published: May 2011

In this paper, we seek to shed new light on the social process of public opinion formation. Drawing on previous contributions in cognition studies and political science, we propose and analyze a model in which heterogeneous agents (citizens) collectively learn and modify their opinions about a specific policy issue. The assumption of nonrationality on the part of agents gives core values, enduring general needs, social interaction, and the combination of the citizens´ intuition and occasional deliberate reasoning a key role in the dynamics of public opinion formation.
Optimal Nonlinear Income Taxation with Habit Formation
Authors: GUO JANG‐TING , KRAUSE ALAN
Published: May 2011

It has recently been shown that incorporating “keeping up with the Joneses” preferences into a prototypical two‐ability‐type optimal nonlinear income tax model leads to higher marginal tax rates for both types of agents. In particular, the high‐skill type faces a positive marginal tax rate, rather than zero as in the conventional case. In this paper, agents’ utility functions are postulated to exhibit “habit formation in consumption” such that the prototypical two‐ability‐type optimal nonlinear income tax model becomes a dynamic analytical framework. We show that if the government can commit to its future fiscal policy, the presence of consumption habits does not affect the standard results on optimal marginal tax rates. By contrast, if the government cannot precommit, the high‐skill type will face a negative marginal tax rate, while the low‐skill type’s marginal tax rate remains positive.
Catching Growth Determinants with the Adaptive Lasso
Authors: Schneider Ulrike , Wagner Martin
Published: May 2011

This paper uses the adaptive Lasso estimator to determine variables important for economic growth. The adaptive Lasso estimator is a computationally very efficient procedure that simultaneously performs model selection and parameter estimation. The computational cost of this method is negligibly small compared with standard approaches in the growth regressions literature. We apply this method for a regional dataset for the European Union covering the 255 NUTS2 regions in the 27 member states over the period 1995-2005. The results suggest that initial GDP per capita (with an implied convergence speed of about 1.5% per annum), human capital ( proxied by the shares of highly and medium educated in the working age population), structural labor market characteristics (the initial unemployment rate and the initial activity rate of the low educated) as well as being a capital region are important for economic growth.
Pain evaluation and control during and following the treatment of hypertrophic scars and keloids by contact and intralesional cryosurgery – a preliminary study
Authors: Mirmovich O. , Gil T. , Goldin I. , Lavi I. , Mettanes I. , Har‐Shai Y.
Published: May 2011

Background  Intralesional cryosurgery effectively treats hypertrophic scars and keloids (HSK), but pain experienced by the patient during treatment can limit the application of cryosurgery.

Objectives  To characterize the pain response during cryosurgical treatment of HSK, and to evaluate the pain experienced during contact and intralesional cryosurgery that employs a pain‐control protocol.

Methods  Twenty‐nine patients (17 women, 12 men) aged 17 years and older (mean ages 31.9 ± 12.5 and 38.9 ± 18.6 years, respectively, P = 0.24), who were treated for a total of 36 HSKs by intralesional (n = 20; 22 cryotreatments) or contact (n = 9; 14 cryotreatments) cryosurgery were evaluated. The pain‐control protocol involved oral pain‐relief tablets (Dipyrone) and translesional local anaesthesia with Bupivacaine hydrochloride 0.5%. Pain evaluation according to the Visual Analogue Scale (VAS) (0–10 cm) was compared between the two groups at three time points: during cryosurgery, immediately after it, and 4 h later. Scores ≤3 cm were considered to define the ‘zone of analgesic success’. These results were compared with control data (contact cryosurgery without a pain‐control protocol; n = 56).

Results  Pain in the intralesional group was significantly lower than that in the contact group during and immediately after cryotreatment. During: mean VAS = 1.68 ± 2.21 vs. 5.07 ± 4.01 cm; median VAS = 0.5 vs. 5.5 cm, respectively; P < 0.0001. Immediately after: mean VAS = 1.22 ± 1.77 vs. 5.38 ± 3.81 cm; median VAS = 0 vs. 6.0 cm, respectively; P = 0.001. The control group had more pain during treatment (mean VAS = 5.34 ± 2.31, median = 6.0) and 4 h later (mean = 3.79 ± 2.35, median = 4.0) than the intralesional group (P < 0.0001 and P = 0.988, respectively). The pain level in the control group during the cryotreatment did not differ from that in the contact group (P = 0.988). In the intralesional, contact and control groups analgesic success (VAS ≤3 cm) was achieved in 77.3%, 35.7% and 33.9%, respectively, of cases (P = 0.002) during cryotreatment, and in 54.5%, 42.9% and 33.9%, respectively, of cases 4 h after treatment (P = 0.24).

Conclusions  The pain‐control protocol significantly reduced pain severity to tolerable levels (VAS ≤3 cm) during and following intralesional and contact cryosurgery. Intralesional cryosurgery caused the least pain during and immediately after treatment.
Patient satisfaction with injection devices: a randomized controlled study comparing two different etanercept delivery systems in moderate to severe psoriasis
Authors: Paul C. , Stalder J.F. , Thaçi D. , Vincendon P. , Brault Y. , Kielar D. , Tebbs V.
Published: May 2011

Background  There is limited information regarding the acceptability of injection devices for biological agents.

Objectives  The primary objective of the study was to investigate patients’ perceptions on the acceptability of two devices delivering etanercept. The secondary objectives of the study were to explore whether patients’ attributes are associated with preferences.

Methods  This was a multicentre, open‐label, randomized, parallel‐design study. Adult patients with psoriasis were randomized to receive etanercept 50 mg twice‐weekly subcutaneously for 12 weeks, either as a pre‐filled syringe or as a pre‐filled pen. The primary outcome was the patient satisfaction at week 12 with the injection device, as measured on a 0–10‐point Likert scale. The study was powered to demonstrate non‐inferiority of a pen over a syringe for the primary endpoint.

Results  A total of 421 patients were randomized. Mean patient satisfaction at week 12 was 8.9 (±1.9) points in the pen group and 7.6 (±2.6) points in the syringe group. There was a statistically significant advantage for the pen compared with the syringe. Multiple correspondence analysis showed that very satisfied patients were the oldest and had had psoriasis for a longer duration, while less satisfied patients were the most anxious and depressed. PASI 75 response was achieved by 61% of patients in the pen group and 57% in the syringe group at week 12.

Conclusions  This study showed higher patient satisfaction when injecting etanercept with a pen compared with a syringe. Factors associated with lower satisfaction are younger age, anxiety and depression.
The relationship between perceived loneliness and cortisol awakening responses on work days and weekends1
Authors: OKAMURA HISAYOSHI , TSUDA AKIRA , MATSUISHI TOYOJIRO
Published: May 2011

The purpose of the present study was to investigate the relationship between the cortisol awakening response (CAR) and perceived loneliness on work days and weekends. Ninety female full‐time workers (20–50 years old) were recruited for this study. Loneliness was evaluated using the Revised UCLA Loneliness Scale, and participants were classified into high (average + 1 SD; n = 20) or low loneliness groups (average – 1 SD; n = 20). The saliva samples were collected on work days and weekends. Participants were instructed to collect saliva on two occasions each day: immediately on awakening and 30 minutes after awakening. The CAR was higher on weekends in the high loneliness group than in the low loneliness group. There were significant differences in the CAR in the low loneliness group between work days and weekends, but not in the high loneliness group. These results indicated that the CAR in high loneliness people was not significantly different between work days and weekends due to a hypothalamic‐pituitary‐adrenal system that is always activated.
Do we need a stressor to be stressed? Insights from cardiac regulation1
Authors: OTTAVIANI CRISTINA , SHAPIRO DAVID
Published: May 2011

In consideration of existing contradictory findings, the aim of the present study was to overcome the limitations of traditional cardiac reactivity studies. First, we examined the cardiac activation that takes place in response to ruminating about stress, independently of the presence of a real stressor, and second, we focused on the underlying physiological components of cardiac regulation during rumination, that is, the sympathetic and parasympathetic components. In 60 participants (27 men and 33 women; mean age = 33.4 ± 9.5 years), we recorded cardiac impedance and heart rate during baseline, an Anger Recall Interview, a reading task, and two recovery periods. Rumination was experimentally manipulated by the use of a distracter. Nondistracted participants showed higher sympathetic activity as suggested by shorter pre‐ejection period, higher low‐frequency heart rate variability (LF‐HRV), higher ratio of LF to high frequency HRV (HF‐HRV), and diminished parasympathetic activity (lower HF‐HRV). The results underscore the association of rumination with a series of well‐known risk factors for health.
The Valuation Accuracy of Equity Value Estimates Inferred from Conventional Empirical Implementations of the Abnormal Earnings Growth Model: US Evidence
Authors: Jorgensen Bjorn N. , Lee Yong Gyu , Yoo Yong Keun
Published: May 2011

Abstract:  We compare the valuation accuracy of the equity value estimates inferred from empirical implementations of the abnormal earnings growth model (Ohlson and Juettner‐Nauroth 2005; the OJ estimates) with the residual income model (Ohlson 1995; the RIV estimates). We find that the OJ estimates generally underperform the RIV estimates. Increasing the forecast horizon for the OJ estimates from two to five years significantly improves their valuation accuracy. However, relative to the RIV estimates, the valuation accuracy of the OJ estimates remains lower even using a five‐year forecast horizon. Finally, we compare predicted accounting profitability with actual accounting profitability and find that the lower valuation accuracy of the OJ estimates is attributable to the empirical assumptions regarding future earnings growth beyond the forecast horizon.
Mandatory IFRS Adoption and Accounting Quality of European Banks
Authors: Gebhardt G¨unther , Novotny‐Farkas Zoltan
Published: May 2011

Abstract:  This paper examines the implications of mandatory IFRS adoption on the accounting quality of banks in twelve EU countries. Specifically, we analyse how the change in the recognition and measurement of banks’ main operating accrual item, the loan loss provision, affects income smoothing behaviour and timely loss recognition. We find that the restriction to recognise only incurred losses under IAS 39 significantly reduces income smoothing. This effect is less pronounced in countries with stricter bank supervision, widely dispersed bank ownership and for EU banks cross‐listed in the US. This provides additional evidence that institutions matter in shaping financial reporting outcomes. Further, the application of the incurred loss approach results in less timely loan loss recognition implying delayed recognition of future expected losses. In the light of the ongoing financial crisis it is questionable whether this is a desirable financial reporting outcome of mandatory IFRS adoption.
The evolution of RNA editing and pentatricopeptide repeat genes
Authors: Fujii Sota , Small Ian
Published: May 2011

The pentatricopeptide repeat (PPR) is a degenerate 35‐amino‐acid structural motif identified from analysis of the sequenced genome of the model plant Arabidopsis thaliana. From the wealth of sequence information now available from plant genomes, the PPR protein family is now known to be one of the largest families in angiosperm species, as most genomes encode 400–600 members. As the number of PPR genes is generally only c. 10–20 in other eukaryotic organisms, including green algae, the family has obviously greatly expanded during land plant evolution. This provides a rare opportunity to study selection pressures driving a 50‐fold expansion of a single gene family. PPR proteins are sequence‐specific RNA‐binding proteins involved in many aspects of RNA processing in organelles. In this review, we will summarize our current knowledge about the evolution of PPR genes, and will discuss the relevance of the dramatic expansion in the family to the functional diversification of plant organelles, focusing primarily on RNA editing.

Contents

Summary
37

I.
Introduction
37

II.
Expansion of the PPR family
38

III.
RNA editing and the evolution of PPR genes
40

IV.
Sequence drift in the organelle genomes of early land plants
41

V.
Loss of RNA editing in angiosperms
43

VI.
Other functions besides editing
44

VII.
Conclusion
44

References
44
Forced‐exercise delays neuropathic pain in experimental diabetes: effects on voltage‐activated calcium channels
Authors: Shankarappa Sahadev A. , Piedras‐Rentería Erika S. , Stubbs Evan B.
Published: May 2011

J. Neurochem. (2011) 118, 224–236.

Physical exercise produces a variety of psychophysical effects, including altered pain perception. Elevated levels of centrally produced endorphins or endocannabinoids are implicated as mediators of exercise‐induced analgesia. The effect of exercise on the development and persistence of disease‐associated acute/chronic pain remains unclear. In this study, we quantified the physiological consequence of forced‐exercise on the development of diabetes‐associated neuropathic pain. Euglycemic control or streptozotocin (STZ)‐induced diabetic adult male rats were subdivided into sedentary or forced‐exercised (2–10 weeks, treadmill) subgroups and assessed for changes in tactile responsiveness. Two weeks following STZ‐treatment, sedentary rats developed a marked and sustained hypersensitivity to von Frey tactile stimulation. By comparison, STZ‐treated diabetic rats undergoing forced‐exercise exhibited a 4‐week delay in the onset of tactile hypersensitivity that was independent of glucose control. Exercise‐facilitated analgesia in diabetic rats was reversed, in a dose‐dependent manner, by naloxone. Small‐diameter (< 30 μm) DRG neurons harvested from STZ‐treated tactile hypersensitive diabetic rats exhibited an enhanced (2.5‐fold) rightward (depolarizing) shift in peak high‐voltage activated (HVA) Ca2+ current density with a concomitant appearance of a low‐voltage activated (LVA) Ca2+ current component. LVA Ca2+ currents present in DRG neurons from hypersensitive diabetic rats exhibited a marked depolarizing shift in steady‐state inactivation. Forced‐exercise attenuated diabetes‐associated changes in HVA Ca2+ current density while preventing the depolarizing shift in steady‐state inactivation of LVA Ca2+ currents. Forced‐exercise markedly delays the onset of diabetes‐associated neuropathic pain, in part, by attenuating associated changes in HVA and LVA Ca2+ channel function within small‐diameter DRG neurons possibly by altering opioidergic tone.
It is still not for the old iron: adjuvant effects of carbonyl iron in experimental autoimmune encephalomyelitis induction
Authors: Miljković Djordje , Momčilović Miljana , Stanojević Željka , Rašić Dejan , Mostarica‐Stojković Marija
Published: May 2011

J. Neurochem. (2011) 118, 205–214.

Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis. Dark Agouti rats immunized with spinal cord homogenate (SCH) and carbonyl iron (CI), as an adjuvant, develop severe hyperacute form of EAE. They succumb to EAE earlier and have higher clinical scores and lethality rate in comparison to counterparts immunized with SCH + complete Freund’s adjuvant. There is no difference in the number of cells or in histological presentation of the CNS infiltrates of rats immunized with the two adjuvants. However, there are more granulocytes, NK and NKT cells, and less CD4+ T cells in the spinal cord infiltrates of SCH + CI‐immunized animals. Nitric oxide (NO)‐generating enzyme inducible NO synthase have higher expression in spinal cord of SCH + CI‐immunized rats, and this corresponds to more intensive nitrotyrosine formation in the CNS tissue of these rats. Abundant infiltration of granulocytes and NK cells into the CNS and excessive generation of peroxynitrite within the CNS of SCH + CI‐immunized rats might account for the severe neurological deficits induced by immunization with CI. These factors should be closely examined in the fulminant forms of multiple sclerosis and acute disseminated encephalomyelitis, as they could represent a promising targets for therapy.
Presumed immune‐mediated hemolytic anemia in two foals withRhodococcus equiinfection
Authors: Johns Imogen C. , Desrochers Anne , Wotman Kathryn L. , Sweeney Raymond W.
Published: May 2011

Objective –To describe the clinical presentation, case management, and outcome in 2 foals withRhodococcus equiinfection associated with presumptive severe immune‐mediated hemolytic anemia.

Series Summary –Two foals diagnosed withR. equipneumonia on the basis of tracheal wash cultures, thoracic radiographs, and thoracic ultrasonography were concurrently diagnosed with hemolytic anemia. Both foals required whole blood transfusions, and were treated with the antimicrobial combination of rifampin and a macrolide (eg, clarithromycin, erythromycin, or azithromycin). Dexamethasone was used to prevent further hemolysis in both foals, and to treat acute lung injury/acute respiratory distress syndrome in 1 of the foals. Both foals survived, and required prolonged antimicrobial therapy.

New or Unique Information Provided –Although extra‐pulmonary disorders are commonly diagnosed in foals infected withR. equi, hemolytic anemia is rarely described. Dexamethasone is considered the treatment of choice for immune‐mediated hemolytic anemia, but may be contra‐indicated in foals with severe bacterial infections. In these foals, a relatively low dose and short duration of dexamethasone was utilized in an attempt to minimize immune suppression, although early discontinuation in 1 foal precipitated a second hemolytic crisis.
Influence of transfusion technique on survival of autologous red blood cells in the dog
Authors: McDevitt Ruth I. , Ruaux Craig G. , Baltzer Wendy I.
Published: May 2011

Objective –To determine the effect of 3 differing transfusion techniques on survival of autologous canine RBCs.

Design –Prospective, blinded study.

Setting –University Teaching Hospital.

Animals –Nine healthy dogs.

Interventions –Three distinct preparations of RBCs, each representing ∼1% of red cell mass, were generated for each dog by biotinylation of RBCs at varying biotin densities. Labeled cells were transfused using 3 techniques (gravity, volumetric pump, syringe pump). Serial determinations of red cell survival were carried out by flow‐cytometric analysis of RBCs collected at 7‐day intervals for 49 days. In vitro analysis of the effect of transfusion methods on RBC integrity and osmotic fragility were carried out in 7/9 dogs.

Measurements and Main Results –RBCs administered via volumetric and syringe pumps exhibited a marked decrease in short‐term probability of survival compared with RBCs delivered by gravity flow. At 24 hours, only 4/8 and 1/7 dogs had surviving cell populations delivered by volumetric and syringe pump, respectively, compared with 8/8 dogs which had surviving cell populations delivered by gravity flow. Circulating half‐life of cells surviving at 24 hours after delivery by volumetric pump was not significantly different to that delivered by gravity flow. No significant effect on in vitro RBC integrity or osmotic fragility was detected in relation to transfusion technique.

Conclusions –Delivery of autologous canine RBCs via mechanical delivery systems was associated with a high risk for early loss of transfused cells.
The anandamide transport inhibitor AM404 reduces the rewarding effects of nicotine and nicotine‐induced dopamine elevations in the nucleus accumbens shell in rats
Authors: Scherma Maria , Justinová Zuzana , Zanettini Claudio , Panlilio Leigh V , Mascia Paola , Fadda Paola , Fratta Walter , Makriyannis Alexandros , Vadivel Subramanian K , Gamaleddin Islam , Le Foll Bernard , Goldberg Steven R
Published: May 2011

BACKGROUND AND PURPOSE The fatty acid amide hydrolase inhibitor URB597 can reverse the abuse‐related behavioural and neurochemical effects of nicotine in rats. Fatty acid amide hydrolase inhibitors block the degradation (and thereby magnify and prolong the actions) of the endocannabinoid anandamide (AEA), and also the non‐cannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). OEA and PEA are endogenous ligands for peroxisome proliferator‐activated receptors alpha (PPAR‐α). Since recent evidence indicates that PPAR‐α can modulate nicotine reward, it is unclear whether AEA plays a role in the effects of URB597 on nicotine reward.

EXPERIMENTAL APPROACH A way to selectively increase endogenous levels of AEA without altering OEA or PEA levels is to inhibit AEA uptake into cells by administering the AEA transport inhibitor N‐(4‐hydroxyphenyl)‐arachidonamide (AM404). To clarify AEA's role in nicotine reward, we investigated the effect of AM404 on conditioned place preference (CPP), reinstatement of abolished CPP, locomotor suppression and anxiolysis in an open field, and dopamine elevations in the nucleus accumbens shell induced by nicotine in Sprague‐Dawley rats.

KEY RESULTS AM404 prevented the development of nicotine‐induced CPP and impeded nicotine‐induced reinstatement of the abolished CPP. Furthermore, AM404 reduced nicotine‐induced increases in dopamine levels in the nucleus accumbens shell, the terminal area of the brain's mesolimbic reward system. AM404 did not alter the locomotor suppressive or anxiolytic effect of nicotine.

CONCLUSIONS AND IMPLICATIONS These findings suggest that AEA transport inhibition can counteract the addictive effects of nicotine and that AEA transport may serve as a new target for development of medications for treatment of tobacco dependence.

LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Tadalafil analgesia in experimental arthritis involves suppression of intra‐articular TNF release
Authors: Rocha FAC , Silva Jr FS , Leite ACRM , Leite AKRM , Girão VCC , Castro RR , Cunha FQ
Published: May 2011

BACKGROUND AND PURPOSE We investigated the effect of the phosphodiesterase‐5 inhibitor, tadalafil, on the acute hypernociception in rat models of arthritis.

EXPERIMENTAL APPROACH Rats were treated with either an intra‐articular injection of zymosan (1 mg) or surgical transection of the anterior cruciate ligament (as an osteoarthritis model). Controls received saline intra‐articular or sham operation respectively. Joint pain was evaluated using the articular incapacitation test measured over 6 h following zymosan or between 4 and 7 days after anterior cruciate ligament transection. Cell counts, tumour necrosis factor‐α (TNF‐α), interleukin‐1 (IL‐1), and the chemokine, cytokine‐induced neutrophil chemoattractant‐1 (CINC‐1) were measured in joint exudates 6 h after zymosan. Groups received tadalafil (0.02–0.5 mg·kg−1per os) or saline 2 h after intra‐articular zymosan. Other groups received the µ‐opioid receptor antagonist naloxone or the cGMP inhibitor 1H‐[1,2,4] oxadiazolo [4,3‐a] quinoxalin‐1‐one (ODQ) before tadalafil.

KEY RESULTS Tadalafil dose‐dependently inhibited hypernociception in zymosan and osteoarthritis models. In zymosan‐induced arthritis, tadalafil significantly decreased cell influx and TNF‐α release but did not alter IL‐1 or CINC‐1 levels. Pretreatment with ODQ but not with naloxone prevented the anti‐inflammatory effects of tadalafil.

CONCLUSIONS AND IMPLICATIONS Therapeutic oral administration of tadalafil provided analgesia mediated by guanylyl cyclase and was independent of the release of endogenous opioids. This effect of tadalafil was associated with a decrease in neutrophil influx and TNF‐α release in inflamed joints.
Constitutive formation of an RXFP1‐signalosome: a novel paradigm in GPCR function and regulation
Authors: Halls Michelle L
Published: May 2011

The classical second messenger cAMP is important in diverse physiological processes, where its spatial and temporal compartmentalization allows precise control over multiple cellular events. Within this context, G‐protein‐coupled receptors (GPCRs) govern specialized pools of cAMP, which are functionally specific for the unique cellular effects attributed to a particular system. The relaxin receptor, RXFP1, is a GPCR that exerts pleiotropic physiological effects including a potent anti‐fibrotic response, increased cancer metastases, and has efficacy as a vasodilator in heart failure. On a cellular level, relaxin stimulation of RXFP1 results in the activation of multiple G‐protein pathways affecting cAMP accumulation. Specificity and diversity in the cAMP signal generated by RXFP1 is controlled by differential G‐protein coupling dependent upon the background of cellular expression, and cAMP compartmentalization. Further complexity in cAMP signalling results from the constitutive assembly of an RXFP1–signalosome, which specifically responds to low concentrations of relaxin, and activates a distinct cAMP pathway. The RXFP1–signalosome is a higher‐order protein complex that facilitates receptor sensitivity to attomolar concentration of peptide, exhibits constitutive activity and dual coupling to G‐proteins and β‐arrestins and reveals a concentration‐biased agonism mediated by relaxin. The specific and directed formation of GPCR‐centered signalosomes allows an even greater spatial and temporal control of cAMP, thus rationalizing the considerable physiological scope of this ubiquitous second messenger.

LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein‐Coupled Receptors (GPCRs). To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐6. To view the 2010 themed section on the same topic visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2010.159.issue‐5/issuetoc
Obesity and risk of vascular disease: importance of endothelium‐dependent vasoconstriction
Authors: Barton Matthias , Baretella Oliver , Meyer Matthias R
Published: May 2011

Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis‐related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium‐derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, ‘premature’ vascular aging. Here, we will review some of the pathomechanisms involved in obesity‐related activation of endothelium‐dependent vasoconstriction, the clinical relevance of obesity‐associated vascular risk, and therapeutic interventions using ‘endothelial therapy’ aiming at maintaining or restoring vascular endothelial health.

LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐3
Reduction of body weight, liver steatosis and expression of stearoyl‐CoA desaturase 1 by the isoflavone daidzein in diet‐induced obesity
Authors: Crespillo A , Alonso M , Vida M , Pavón FJ , Serrano A , Rivera P , Romero‐Zerbo Y , Fernández‐Llebrez P , Martínez A , Pérez‐Valero V , Bermúdez‐Silva FJ , Suárez J , de Fonseca FR
Published: May 2011

BACKGROUND AND PURPOSE The lack of safe and effective treatments for obesity has increased interest in natural products that may serve as alternative therapies. From this perspective, we have analysed the effects of daidzein, one of the main soy isoflavones, on diet‐induced obesity in rats.

EXPERIMENTAL APPROACH Rats made obese after exposure to a very (60%) high fat‐content diet were treated with daidzein (50 mg·kg−1) for 14 days. The dose was selected on the basis of the acute effects of this isoflavone on a feeding test. After 14 days, animals were killed and plasma, white and brown adipose tissue, muscle and liver studied for the levels and expression of metabolites, proteins and genes relevant to lipid metabolism.

KEY RESULTS A single treatment (acute) with daidzein dose‐dependently reduced food intake. Chronic treatment (daily for 14 days) reduced weight gain and fat content in liver, accompanied by high leptin and low adiponectin levels in plasma. While skeletal muscle was weakly affected by treatment, both adipose tissue and liver displayed marked changes after treatment with daidzein, affecting transcription factors and lipogenic enzymes, particularly stearoyl coenzyme A desaturase 1, a pivotal enzyme in obesity. Expression of uncoupling protein 1, an important enzyme for thermogenesis, was increased in brown adipose tissue after daidzein treatment.

CONCLUSIONS AND IMPLICATIONS These results support the use of isoflavones in diet‐induced obesity, especially when hepatic steatosis is present and open a new field of use for these natural products.
Effects of Visiting Nurses' Individually Tailored Education for Low‐Income Adult Diabetic Patients in Korea
Authors: Ko Il Sun , Lee Tae Hwa , Kim Gwang Suk , Kang Se Won , Kim Mi Ja
Published: May 2011

ABSTRACT Objective: To describe the effects of individually tailored education by visiting nurses for low‐income adult diabetic patients.

Design and Sample: This one‐group pretest‐posttest study included 96 newly registered low‐income adult diabetic patients in a public health center in DJ‐gu (similar to a county in the United States) in 2006; the patients met the selection criteria.

Measures: Diabetes knowledge, self‐management, and blood glucose levels were compared before and after education.

Intervention: 15 visiting nurses delivered individually tailored education for 60–90 min/month for 7 months.

Results: After education, diabetes knowledge (p<.001) and self‐management in all categories of lifestyle (p<.001), diet (p<.001), exercise (p<.001), foot care (p<.001), medication (p=.004), and insulin therapy (p=.022) significantly improved. The mean fasting blood glucose (FBG) level decreased by 14.53 mg/dl; this decrease was insignificant (p=.117). However, the relationship between education and FBG levels was significant (χ2=40.11, p=.005).

Conclusions: Tailored education effectively improved the patients' knowledge of diabetes and self‐management. Therefore, regular, individually tailored education on a long‐term basis by visiting nurses can provide essential education to low‐income adult diabetic patients for maintaining self‐management.
Disappearing Décalage: Object Search in Light and Dark at 6 Months
Authors: Shinskey Jeanne L.
Published: May 2011

Infants search for an object hidden by an occluder in the light months later than one hidden by darkness. One explanation attributes this décalage to easier action demands in darkness versus occlusion, whereas another attributes it to easier representation demands in darkness versus occlusion. However, search tasks typically confound these two types of demands. This article presents a search task that unconfounds them to better address these two explanations of the “dark advantage.” Objects were hidden by submersion in liquid instead of occlusion with a screen, allowing infants to search with equally simple actions in light versus dark. In Experiment 1, 6‐month‐olds unexpectedly showed a dark disadvantage by discriminating when an object was hidden in the light but not the dark. Experiment 2 addressed the possibility that representation demands were higher in the dark than the light and showed that infants’ search in the dark increased to match that in the light, but not exceed it. Six‐month‐olds can thus search for a hidden object both when action demands are simplified and when a noncohesive substance rather than a cohesive occluder hides the object, supporting aspects of both action‐demand and representation‐demand explanations of décalage in search behavior.
Male antagonistic behaviour after spawning suggests paternal care in brown trout, Salmo trutta
Authors: Tentelier Cédric , Larrieu Maider , Aymes Jean‐Christophe , Labonne Jacques
Published: May 2011

Abstract –  The evolution of parental care depends on the sex‐dependent resolution of a trade‐off between present and future reproduction. In salmonids, the mating systems are often characterised by fierce male–male competition, and the absence of paternal care is widely admitted in these species. However, the fact that brown trout eggs can be cannibalised by peripheral individuals just after spawning suggests that dominant males would benefit from protecting their offspring by keeping cannibals away from the nest. We used 77 field observations of brown trout spawning to document the defensive behaviour of dominant males towards peripheral individuals before and after spawning, and test whether this behaviour was related to the probability of the clutch being cannibalised. We showed that dominant males stayed on the nest and chased peripherals even after the eggs were laid and fertilised. The number of chases performed by dominant males during the 2 min following spawning was negatively correlated to the probability of egg cannibalism. This result indicates that brown trout males can provide direct benefits to females through protection against egg cannibalism by peripheral individuals.