bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients
Authors: Schmidt Enno , Dähnrich Cornelia , Rosemann Anke , Probst Christian , Komorowski Lars , Saschenbrecker Sandra , Schlumberger Wolfgang , Stöcker Winfried , Hashimoto Takashi , Bröcker Eva‐Bettina , Recke Andreas , Rose Christian , Zillikens Detlef
Published: February 2010

Please cite this paper as: Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Experimental Dermatology 2010; 19: 458–463.

Abstract:  Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are intraepidermal blistering skin diseases. PV is characterised by autoantibodies directed against desmoglein (Dsg) 3 and in patients with the mucocutaneous variant also against Dsg 1, whereas in PF, only Dsg 1 is targeted. Here, ectodomains of Dsg 3 and Dsg 1 were recombinantly expressed in a human cell line (HEK293) and applied as authentic solid phases in ELISA test systems. Autoantibodies against Dsg 3 and/or Dsg 1 could be detected in 71 (100%) of 71 PV sera and against Dsg 1 in 48 (96%) of 50 PF sera. Control sera showed reactivity with Dsg 3 and Dsg 1 in 0.2% and 0.7%, respectively, of 401 healthy blood donors and in 2.1% of 48 randomly selected patients with bullous pemphigoid. No reactivity with Dsg 1 and 3 was detected in 21 patients with linear IgA disease. For both pemphigus variants, a statistically significant correlation between clinical severity and autoantibody levels was observed as demonstrated for 10 PV and 5 PF patients. In conclusion, the use of the ectodomains of Dsg 3 and 1 as target antigens expressed in a human cell line resulted in sensitive and specific ELISA systems for both diagnosis and monitoring of PV and PF.
Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL‐37 in human dermal fibroblasts
Authors: Park Hyun Jeong , Ock Sun Myeong , Kim Hee Jung , Park Hong Jin , Lee Young Bok , Choi Jung Min , Cho Chul Soo , Lee Jun Young , Cho Baik Kee , Cho Dae Ho
Published: February 2010

Please cite this paper as: Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL‐37 in human dermal fibroblasts. Experimental Dermatology 2010; 19: e258–e264.

Abstract:  Vitamin C is used as an anti‐ageing agent because of its collagen enhancing effects. The precise cellular signalling mechanism of vitamin C is not well known. Here, we investigate the profibrotic mechanism of vitamin C against LL‐37. Antimicrobial peptide LL‐37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL‐37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal‐regulated kinase (ERK). HDFs and human keloid fibroblasts were treated with vitamin C followed by 2 h of LL‐37 treatment. Collagen mRNA expression and total soluble collagen production inhibited by LL‐37 was enhanced by treatment with 0.5 mm vitamin C. Vitamin C also decreased intracellular reactive oxygen intermediates (ROI) levels that were increased by LL‐37. Furthermore, the phosphorylation of ERK was analysed by Western blot following treatment with vitamin C and LL‐37. Vitamin C turned off phosphorylation of ERK that was induced by LL‐37. Ets‐1 transcriptional factor, which is involved in the regulation of collagen expression by LL‐37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL‐37.
REVIEW ARTICLE: Interleukin‐10: A Multi‐Faceted Agent of Pregnancy
Authors: Thaxton Jessica E. , Sharma Surendra
Published: February 2010

Citation Thaxton JE, Sharma S. Interleukin‐10: a multi‐faceted agent of pregnancy. Am J Reprod Immunol 2010

It is widely accepted that pregnancy constitutes a unique developmental event. Unprecedented intrauterine actions of angiogenesis, immunity, and neuroendocrine regulation are juxtaposed to mechanisms of senescence that enable fetal growth and protection. The suppressive and regulatory factors that facilitate healthy pregnancy are under investigation. In non‐pregnant systems of infection and inflammation, the cytokine interleukin‐10 (IL‐10) has been widely investigated because of its potential as a key immunosuppressant in response to a multitude of inflammatory events. In the context of pregnancy, IL‐10 levels increase markedly in women during early pregnancy and remain elevated well into the third trimester immediately prior to onset of labor. The role of IL‐10 during pregnancy as a suppressor of active maternal immunity to allow acceptance of the fetal allograft has been a point of study. Moreover, secretion of IL‐10 by a diverse set of maternal and fetal cells has proven to aid in the orchestration of normal processes of pregnancy. Interestingly, some of the more profound findings regarding the actions of IL‐10 during pregnancy have manifested from research that focuses on aberrant pregnancy outcomes as a result of inflammation, hormonal imbalances, or gene–environment interactions. This review focuses on the role of IL‐10 as a facilitator of successful pregnancy both as an immune suppressive agent and a mediator of cross talk between the placenta and the decidua. Importantly, we discuss investigations on adverse pregnancy conditions to further elucidate the multifarious role of IL‐10 at the maternal–fetal interface.
DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in schizophrenic patients – support for the glutamate hypothesis of schizophrenias
Authors: Fallgatter A. J. , Ehlis A.‐C. , Herrmann M. J. , Hohoff C. , Reif A. , Freitag C. M. , Deckert J.
Published: February 2010

Dysbindin (DTNBP1) is a recently characterized protein that seems to be involved in the modulation of glutamatergic neurotransmission in the human brain, thereby influencing prefrontal cortex function and associated cognitive processes. While association, neuroanatomical and cellular studies indicate that DTNBP1 might be one of several susceptibility genes for schizophrenia, the effect of dysbindin on prefrontal brain function at an underlying neurophysiological level has not yet been explored for these patients. The NoGo‐anteriorization (NGA) is a topographical event‐related potential measure, which has been established as a valid neurophysiological marker of prefrontal brain function. In the present study, we investigated the influence of seven dysbindin gene variants on the NGA in a group of 44 schizophrenic patients. In line with our a priori hypothesis, one DTNBP1 polymorphism previously linked to schizophrenia (rs2619528) was found to be associated with changes in the NGA; however, the direction of this association directly contrasts with our previous findings in a healthy control sample. This differential impact of DTNBP1 gene variation on prefrontal functioning in schizophrenic patients vs. healthy controls is discussed in terms of abnormal glutamatergic baseline levels in patients suffering from schizophrenic illnesses. This is the first report on a role of DTNBP1 gene variation for prefrontal functioning at a basic neurophysiological level in schizophrenic patients. An impact on fundamental processes of cognitive response control may be one mechanism by which DTNBP1 gene variants via glutamatergic transmission contribute to the pathophysiology underlying schizophrenic illnesses.
Children are reliable reporters of common symptoms: results from a self‐reported symptom diary for primary school children
Authors: Lundqvist C , Rugland E , Clench‐Aas J , Bartonova A , Hofoss D
Published: February 2010

Background:  Collecting information on subjective symptoms in children by parental reports or physician’s interview is indirect and not suited for prospective data collection over extended time periods.

Aim:  To examine the reliability of a diary for symptom self‐reports by primary school children.

Methods:  Children aged 7–8 or 11–12 were recruited from primary school and a paediatric outpatient department. A picture‐based symptom diary was completed individually. Children were asked about presence of 10 specified subjective symptoms for five time periods covering the previous 24 h. The diary was completed twice for test–retest and answers were compared with semi structured physician’s interviews.

Results:  Test–retest reliability for reporting a symptom during the previous 24 h gave reliable kappa values of 0.64–0.91. Comparison with physician’s interview gave kappas of 0.18–0.68. Requiring correct time of day for each symptom reduced reliability and validity. Kappa values for test–retest and child‐physician agreement for the individual symptoms were respectively: sneezing, 0.80 and 0.30; sore throat, 0.89, 0.30; tiredness, 0.88, 0.65; headache, 0.64, 0.66; runny nose, 0.91, 0.68; sore eyes, 0.67, 0.18; cough, 0.73, 0.58; stomach ache, 0.69, 0.45.

Conclusion:  Our symptom diary gives reliable self‐report data from primary school children. It may be used for prospective symptom monitoring.
An estrogen receptor α suppressor, microRNA‐22, is downregulated in estrogen receptor α‐positive human breast cancer cell lines and clinical samples
Authors: Xiong Jianhua , Yu Dianke , Wei Na , Fu Hanjiang , Cai Tianjing , Huang Yuanyu , Wu Chen , Zheng Xiaofei , Du Quan , Lin Dongxin , Liang Zicai
Published: February 2010

Previous studies have suggested that microRNAs (miRNAs) may play important roles in tumorigenesis, but little is known about the functions of most miRNAs in cancer development. In the present study, we set up a cell‐based screen using a luciferase reporter plasmid carrying the whole ∼ 4.7 kb 3′‐UTR of estrogen receptor α (ERα) mRNA cotransfected with a synthetic miRNA expression library to identify potential ERα‐targeting miRNAs. Among all the miRNAs, miR‐22 was found to repress robustly the luciferase signal in both HEK‐293T and ERα‐positive MCF‐7 cells. Mutation of the target site was found to abrogate this repression effect of miR‐22, whereas antagonism of endogenous miR‐22 in MDA‐MB‐231 cells resulted in elevated reporter signals. We assessed the miR‐22 expression patterns in five breast cancer cell lines and 23 clinical biopsies and revealed that there is a significant inverse association between the miR‐22 levels and ERα protein expression. To evaluate the potential of miR‐22 as a potential therapeutic intervention, we found that reduction of endogenous ERα protein levels and suppression of cancer cell growth could be achieved in MCF‐7 cells by miR‐22 overexpression in a way that can be recapitulated by the introduction of specific small interfering RNA against ERα. The phenomena can be rescued by the reintroduction of ERα. Taken together, our data indicate that miR‐22 was frequently downregulated in ERα‐positive human breast cancer cell lines and clinical samples. Direct involvement in the regulation of ERα may be one of the mechanisms through which miR‐22 could play a pivotal role in the pathogenesis of breast cancer.
On sustained economic growth with wealth effects
Authors: Roy Santanu
Published: February 2010

In a discounted one‐sector convex model of optimal economic growth where utility may depend on both consumption and capital stock, I derive necessary and sufficient conditions for sustained growth (unbounded expansion of capital and consumption). Conditions for bounded growth and extinction are also outlined. Optimal paths may be non‐monotone. Sustained growth may occur even though the asymptotic marginal productivity is less than the discount rate and may require the initial capital stock to be above a critical level. The behavior of the marginal rate of substitution between consumption and capital plays a crucial role in the conditions.
Literacy traps: Society‐wide education and individual skill premia
Authors: Atal Vidya , Basu Kaushik , Gray John , Lee Travis
Published: February 2010

Using a model of an O‐ring production function, the present paper demonstrates how certain communities can get caught in a low‐literacy trap in which each individual finds that it is not worthwhile investing in higher skills because others are not high‐skilled. The model sheds light on educational policy. It is shown that policy for promoting human capital has to take the form of a mechanism for solving the coordination failure in people's choice of educational strategy.
‘Building a Future for Wildlife’? Evaluating the contribution of the world zoo and aquarium community to in situ conservation
Authors: GUSSET M. , DICK G.
Published: February 2010

In light of the United Nations declaring 2010 as the ‘International Year of Biodiversity’, we carried out an audit of in situ conservation projects supported by the world zoo and aquarium community. The results of our questionnaire survey show that the 113 evaluated projects are helping to improve the conservation status of high‐profile threatened species and habitats in biodiversity‐rich regions of the world. Our results show that thanks to the investment made by zoos and aquariums, particularly financial, these projects reached overall impact scores of a magnitude suggestive of an appreciable contribution to global biodiversity conservation. The present first global appraisal of the contribution of the world zoo and aquarium community to in situ conservation from a supported project's perspective thus suggests that zoos and aquariums are on track for ‘Building a Future for Wildlife’, as stipulated in the revised World Zoo and Aquarium Conservation Strategy of 2005. However, zoos and aquariums could make an even stronger contribution by allocating more resources to in situ conservation, which – as our results show – would significantly increase the projects' conservation impact. Increased pooling of resources among zoological institutions thus appears to be advisable.
Small canid husbandry challenges: reviewing problems, with recommendations for improving captive canid programmes
Authors: BAUMAN K. , MEKARSKA A. , GRISHAM J. , LYNCH C.
Published: February 2010

Small canids (≤10 kg) represent a diverse group of species that have been a part of collections before zoos first opened to the public in the late 18th and the 19th centuries. Twentieth‐century zoos have changed the way species are managed with a focus on conservation programmes. Large‐canid programmes have flourished but the development of programmes for small‐canid species has been slower. In the last decade, zoos have increased their work with small‐canid species creating several conservation programmes and more are proposed in the future. However, these programmes still have several obstacles to overcome, including the dearth of data available from in situ populations, the need to refine (or develop) husbandry protocols, inconsistent reproduction, limited space and uninspiring exhibits. Nonetheless each of these areas represents opportunities for shaping the future of how ex situ populations of small canids will play a role in global conservation efforts. In this article, we review the history of small‐canid species in captivity, drawing on examples from the Association of Zoos and Aquariums and the European Association of Zoos and Aquaria. Within this context, we highlight work that remains to be done and challenges that must be overcome to improve conservation of small‐canid species.
Impaired cardiac functional reserve in type 2 diabetic db/db mice is associated with metabolic, but not structural, remodelling
Authors: Daniels A. , Van Bilsen M. , Janssen B. J. A. , Brouns A. E. , Cleutjens J. P. M. , Roemen T. H. M. , Schaart G. , Van Der Velden J. , Van Der Vusse G. J. , Van Nieuwenhoven F. A.
Published: February 2010

Aim:  To identify the initial alterations in myocardial tissue associated with the early signs of diabetic cardiac haemodynamic dysfunction, we monitored changes in cardiac function, structural remodelling and gene expression in hearts of type 2 diabetic db/db mice.

Methods:  Cardiac dimensions and function were determined echocardiographically at 8, 12, 16 and 18 weeks of age. Left ventricular pressure characteristics were measured at 18 weeks under baseline conditions and upon dobutamine infusion.

Results:  The db/db mice were severely diabetic already at 8 weeks after birth, showing elevated fasting blood glucose levels and albuminuria. Nevertheless, echocardiography revealed no significant changes in cardiac function up to 18 weeks of age. At 18 weeks of age, left ventricular pressure characteristics were not significantly different at baseline between diabetic and control mice. However, dobutamine stress test revealed significantly attenuated cardiac inotropic and lusitropic responses in db/db mice. Post‐mortem cardiac tissue analyses showed minor structural remodelling and no significant changes in gene expression levels of the sarcoplasmic reticulum calcium ATPase (SERCA2a) or β1‐adrenoceptor (β1‐AR). Moreover, the phosphorylation state of known contractile protein targets of protein kinase A (PKA) was not altered, indicating unaffected cardiac β‐adrenergic signalling activity in diabetic animals. By contrast, the substantially increased expression of uncoupling protein‐3 (UCP3) and angiopoietin‐like‐4 (Angptl4), along with decreased phosphorylation of AMP‐activated protein kinase (AMPK) in the diabetic heart, is indicative of marked changes in cardiac metabolism.

Conclusion:  db/db mice show impaired cardiac functional reserve capacity during maximal β‐adrenergic stimulation which is associated with unfavourable changes in cardiac energy metabolism.
Assessment of current disease surveillance activities for pigs post‐farmgate in New South Wales
Authors: Schemann AK , Hernández‐Jover M , Hall W , Holyoake PK , Toribio J‐ALML
Published: February 2010

Objectives  Evaluate current disease surveillance activities at saleyards and abattoirs in New South Wales (NSW) in order to establish the prevalence of clinical anomalies in pigs at different sites and to compare the sensitivity of detecting anomalies inside versus outside of pens.

Procedure  Routine inspections of pigs by staff and government inspectors were observed at two saleyards and two abattoirs in NSW during three visits over a 2‐month period (January 2008–March 2008). All pigs presented for sale or slaughter were examined for 19 clinical anomalies from either the side of the pen or while animals were moving outside the pen, with data being combined to give an assumed ‘gold standard’. We compared the prevalence of anomalies among animals at the four sites using logistic regression, as well as the sensitivity of detection of the two inspection methods.

Results  Frequency and methodology of routine inspection varied among sites. Of the 7747 pigs inspected, 822 (10.6%) showed at least one clinical anomaly. There was moderate agreement between detecting anomalies in penned pigs versus while being moved. Pigs at one abattoir exhibited significantly fewer anomalies than pigs at the other sites.

Conclusion  The prevalence of anomalies among pigs at saleyards and abattoirs in NSW was relatively high (≈10%). Weaknesses in current disease surveillance activities for pigs post‐farmgate have been identified. Increased regulation, surveillance training and modification of standard operational procedures for inspection have the potential to improve the current system.
Isolation of bovine herpesvirus type 5 from the semen of a healthy bull in Australia
Authors: Diallo IS , Hewitson GR , Hoad J , Turner S , Corney BG , Rodwell BJ
Published: February 2010

Artificial insemination is widely used in the cattle industry and a major challenge is to ensure that semen is free of infectious agents. A healthy donor bull was tested for freedom from infectious agents. A bovine herpesvirus was isolated in testis cells and identified as bovine herpesvirus type 5 (BoHV‐5) by polymerase chain reaction and by direct amplicon sequencing. The amplicon sequence shared 100% similarity with the published sequence of BoHV‐5. This is the first report in Australia of BoHV‐5 in semen. The implications of this finding are discussed.
Topical anaesthesia alleviates short‐term pain of castration and tail docking in lambs
Authors: Lomax S , Dickson H , Sheil M , Windsor PA
Published: February 2010

Objective  To investigate the effect of a topical anaesthetic formulation on pain alleviation, wound healing and systemic levels of local anaesthetic actives in lambs undergoing castration and tail docking.

Design  Three placebo‐controlled and/or randomised experiments were conducted using three groups of Merino lambs (n = 62, 68 and 19) undergoing routine castration and tail docking.

Procedure  Surgical castration, with either surgical or hot‐iron tail docking, was performed with and without the application of topical anaesthetic (Tri‐Solfen®) or placebo. The effects of this procedure were compared with those of rubber ring castration and tail docking, and of the handled but unmarked controls. Wound pain was assessed using calibrated Von‐Frey monofilaments over a 4‐h period, pain‐related behaviour was assessed over 5 h, wound healing was assessed at 14 and 28 days, and the plasma levels of lignocaine and bupivacaine were determined.

Results  Rapid and up to 4 h primary hyperalgesia developed following surgical castration and tail docking in the untreated and placebo‐treated lambs. It was absent in the castration wounds, and significantly reduced in the tail‐docking wounds, of the treated lambs. Hot‐iron docking was associated with mild and transient secondary hyperalgesia, which was abolished by the topical anaesthesia. There was a significant reduction in pain‐related behaviours in treated lambs, which were not significantly different in their behaviour to the sham‐operation handled controls. Plasma lignocaine and bupivacaine levels were below the toxic thresholds in all tested lambs.

Conclusion  Topical anaesthesia alleviates wound pain and significantly reduces pain‐related behaviours in lambs undergoing surgical castration plus surgical or hot‐iron tail docking, without a negative effect on wound healing or a risk of systemic toxicity.
Nasal vascular hamartoma in a Domestic Shorthair cat
Authors: Chambers BA , Laksito MA , Fliegner RA , McCowan C , Beck C , Yates GD
Published: February 2010

A nasal mass in a Domestic Shorthair cat was causing facial deformity, sneezing and intermittent epistaxis. Biopsy samples obtained previously had been non‐diagnostic. Computed tomography images revealed an irregular, contrast‐enhancing mass occupying a large portion of the righthand side of the nasal cavity. Previously described criteria for malignancy were not present. A ventral surgical approach combined with temporary, ipsilateral, common carotid arterial occlusion provided excellent access for debulking the lesion and collecting samples for histopathology. A nasal vascular hamartoma was diagnosed and clinical signs resolved postoperatively. This is the first documentation of this abnormality in the cat. Hamartomatous abnormalities should be included on the list of differential diagnoses for feline nasal mass lesions. The prognosis for hamartomatous lesions postoperatively is good, in keeping with their limited propensity for growth after maturity.
Molecular Detection of Crimean‐Congo Haemorrhagic Fever Virus (CCHFV) but not West Nile Virus (WNV) in Hard Ticks from Provinces in Northern Turkey
Authors: Albayrak H. , Ozan E. , Kurt M.
Published: February 2010

In this study, the hard ticks collected from a variety of mammalian species (cattle, sheep, goat, buffalo) and a turtle in either coastal or inland Black Sea region of Turkey were surveyed for the presence of RNA from Crimean‐Congo haemorrhagic fever virus (CCHFV) and West Nile virus (WNV). No WNV genomic RNA was detected in any tick sample. However, CCHFV RNA was found in 29 of 421 tick pools (6.88%). Positivity rates for the provinces varied and were as follows: Samsun 4.38%; Ordu 4.34%; Giresun 6.32%; Sinop 14.63%; Amasya 5.55%; Tokat 3.38% and Sivas 4.83%. Crimean‐Congo haemorrhagic fever virus genomic RNA was detected in seven of eleven tick species tested. These results suggest that these hard ticks may act as a reservoir for CCHFV in northern Turkey, but probably have no role in WNV transmission.
Evaluation of Pet‐Related Management Factors and the Risk of Salmonella spp. Carriage in Pet Dogs from Volunteer Households in Ontario (2005–2006)
Authors: Leonard E. K. , Pearl D. L. , Finley R. L. , Janecko N. , Peregrine A. S. , Reid‐Smith R. J. , Weese J. S.
Published: February 2010

The purpose of this study was to determine pet‐related management factors that may be associated with the presence of Salmonella spp. in feces of pet dogs from volunteer households. From October 2005 until May 2006, 138 dogs from 84 households in Ontario were recruited to participate in a cross‐sectional study. Five consecutive daily fecal samples were collected from each dog and enrichment culture for Salmonella spp. was performed. A higher than expected number of the dogs (23.2%; 32/138) had at least one fecal sample positive for Salmonella, and 25% (21/84) of the households had at least one dog shedding Salmonella. Twelve serotypes of Salmonella enterica subsp. enterica were identified, with the predominant serotypes being Typhimurium (33.3%; 13/39), Kentucky (15.4%; 6/39), Brandenburg (15.4%; 6/39) and Heidelberg (12.8%; 5/39). Univariable logistic regression models were created with a random effect for household to account for clustering. Statistically significant risk factors for a dog testing positive included having contact with livestock, receiving a probiotic in the previous 30 days, feeding a commercial or homemade raw food diet, feeding raw meat and eggs, feeding a homemade cooked diet, and having more than one dog in the household. In two‐variable models that controlled for feeding raw food, the non‐dietary variables were no longer statistically significant. These results highlight the potential public health risk of including raw animal products in canine diets.
Nationwide Surveillance of West Nile Virus Targeting Mosquitoes and Dead Birds from April 2004 through March 2007 in Japan
Authors: Shirafuji H. , Kanehira K. , Nishiguchi A. , Kamio T.
Published: February 2010

We conducted nationwide West Nile virus (WNV) surveillance targeting mosquitoes and dead birds to reveal whether the virus and its potential vectors are present in Japan. A total of 12 766 mosquitoes and 230 dead birds were collected in April 2004–March 2005 (the 2004–2005 period), 10 755 mosquitoes and 267 dead birds in April 2005–March 2006 (the 2005–2006 period), and 8624 mosquitoes and 245 dead birds in April 2006–March 2007 (the 2006–2007 period). The species of most of the mosquitoes collected over the 3 years were Culex tritaeniorhynchus (47.82%) and Anopheles sinensis (28.49%), and other species included Aedes albopictus (6.75%), the Culex pipiens group (Cx. pipiens pallens and Cx. pipiens molestus: 5.37%), Aedes vexans nipponii (2.54%), Armigeres subalbatus (1.08%), and Aedes japonicus (0.95%). As for the dead birds, most were Passeriformes (456 specimens), which included several crow species, and the other orders included Anseriformes, Columbiformes and Ciconiiformes (78, 66 and 36 specimens, respectively). All the specimens tested negative for WNV RNA by reverse‐transcriptase polymerase chain reaction (RT‐PCR) in the 2004–2005 period and by real‐time RT‐PCR in the 2005–2006 and the 2006–2007 periods, respectively. Our surveillance provided no evidence for WNV in Japan as of the end of the surveillance period, but on the other hand, it revealed that several species of potential WNV vectors are distributed widely in Japan, which suggests that WNV in principle could be transmitted by the potential vectors if introduced. Thus, it is essential to take continued precautions against WNV introduction.
No Emergence of Echinococcus multilocularis in Foxes in Flanders and Brussels Anno 2007–2008
Authors: Van Gucht S. , Van Den Berge K. , Quataert P. , Verschelde P. , Le Roux I.
Published: February 2010

Echinococcus multilocularis is highly endemic in red foxes in southern Belgium (region of Wallonia), especially in the higher located forested areas. The north of Belgium, including the regions of Flanders and Brussels, is more urbanized and has been colonized entirely by red foxes since the 1980s. A temperospatial analysis of compiled epidemiological data from 1996 to 2003 predicted a northwest spread of the cestode from Wallonia and the Netherlands towards Flanders and Brussels (Prev. Vet. Med. 2006, 76, 137–150). In 2007–2008, none of 187 examined foxes from the north tested positive (<2.8%, α = 0.01), compared to 1.7% in 1996–1999. This suggests that the parasite is not emerging in the examined area and the endemic region has not significantly extended northwest during the last decade. The possible reasons are discussed in the article, including the relatively low altitude, milder climate or low abundance of suitable intermediate hosts. The low prevalence in foxes and the generally low infection rate in humans imply that the risk for public health in Flanders and Brussels is limited anno 2007–2008.
On the Relationships Among Strouhal Number, Pressure Drag, and Separation Pressure for Blocked Bluff-Body Flow
Authors: Yeung W. W. H.
Published: February 2010

Strouhal number, pressure drag, and separation pressure are some of the intrinsic parameters for investigating the flow around a bluff-body. An attempt is made to formulate a relationship involving these quantities for flow around a two-dimensional bluff section of various shapes in a confined environment such as a wind tunnel. It includes (a) establishing a relation between the Strouhal number and a modified Strouhal number by a theoretical wake width and (b) incorporating this wake width into a momentum equation to determine the pressure drag. Comparisons have been made with the experimental data, a theoretical prediction (for unconfined flow), and an empirical proposal in literature to indicate that the present methodology is appropriate. Together with its extension to axisymmetric bodies, the current method is able to provide proper limits to the experimental data for a rectangular flat-plate of various width-to-span ratios. In addition, if the separation pressure is given, then the Strouhal number is inversely proportional to the drag coefficient, being comparable to a proposal based on statistical results. Finally, through an example, it is also demonstrated how one of these three parameters may be reasonably estimated from the measured values of the other two.
An Experimental Investigation for Bubble Rising in Non-Newtonian Fluids and Empirical Correlation of Drag Coefficient
Authors: Wenyuan Fan , Youguang Ma , Shaokun Jiang , Ke Yang , Huaizhi Li
Published: February 2010

The velocity, shape, and trajectory of the rising bubble in polyacrylamide (PAM) and carboxymethylcellulose (CMC) aqueous solutions were experimentally investigated using a set of homemade velocimeters and a video camera. The effects of gas the flowrate and solution concentration on the bubble terminal velocity were examined respectively. Results show that the terminal velocity of the bubble increases with the increase in the gas flowrate and the decrease in the solution concentration. The shape of the bubble is gradually flattened horizontally to an ellipsoid with the increase in the Reynolds number (Re), Eötvös number (Eo), and Morton number (Mo). With the increase in the Re and Eo, the rising bubble in PAM aqueous solutions begin to oscillate, but there is no oscillation phenomena for CMC aqueous solutions. By dimensional analysis, the drag coefficient of a single bubble in non-Newtonian fluids in a moderate Reynolds number was correlated as a function of Re, Eo, and Archimedes number (Ar) based on the equivalent bubble diameter. The predicted results by the present correlation agree well with the experimental data.
Wave Propagation in Thin-Walled Aortic Analogues
Authors: Giannopapa C. G. , Kroot J. M. B. , Tijsseling A. S. , Rutten M. C. M. , van de Vosse F. N.
Published: February 2010

Research on wave propagation in liquid filled vessels is often motivated by the need to understand arterial blood flows. Theoretical and experimental investigation of the propagation of waves in flexible tubes has been studied by many researchers. The analytical one-dimensional frequency domain wave theory has a great advantage of providing accurate results without the additional computational cost related to the modern time domain simulation models. For assessing the validity of analytical and numerical models, well defined in vitro experiments are of great importance. The objective of this paper is to present a frequency domain analytical model based on the one-dimensional wave propagation theory and validate it against experimental data obtained for aortic analogs. The elastic and viscoelastic properties of the wall are included in the analytical model. The pressure, volumetric flow rate, and wall distention obtained from the analytical model are compared with experimental data in two straight tubes with aortic relevance. The analytical results and the experimental measurements were found to be in good agreement when the viscoelastic properties of the wall are taken into account.
Experimental Study of a Cavitating Centrifugal Pump During Fast Startups
Authors: Duplaa S. , Coutier-Delgosha O. , Dazin A. , Roussette O. , Bois G. , Caignaert G.
Published: February 2010

The startup of rocket engine turbopumps is generally performed only in a few seconds. It implies that these pumps reach their nominal operating conditions after only a few rotations. During these first rotations of the blades, the flow evolution in the pump is governed by transient phenomena, based mainly on the flow rate and rotation speed evolution. These phenomena progressively become negligible when the steady behavior is reached. The pump transient behavior induces significant pressure fluctuations, which may result in partial flow vaporization, i.e., cavitation. An existing experimental test rig has been updated in the LML Laboratory (Lille, France) for the startups of a centrifugal pump. The study focuses on the cavitation induced during the pump startup. Instantaneous measurement of torque, flow rate, inlet and outlet unsteady pressures, and pump rotation velocity enable to characterize the pump behavior during rapid starting periods. Three different types of fast startup behaviors have been identified. According to the final operating point, the startup is characterized either by a single drop of the delivery static pressure, by several low-frequency drops, or by a water hammer phenomenon that can be observed in both the inlet and outlet of the pump. A physical analysis is proposed to explain these three different types of transient flow behavior.
A Single-Stage Centripetal Pump—Design Features and an Investigation of the Operating Characteristics
Authors: Sekavčnik Mihael , Gantar Tine , Mori Mitja
Published: February 2010

In this paper, we present an experimental and numerical investigation of a single-stage centripetal pump (SSCP). This SSCP is designed to operate in the pump regime, while forcing the working media through impeller-stator flow channels in the radial inward direction. The measured performance curves are characterized by a hysteresis, since the throttle-closing performance curves do not correspond to the throttle-opening performance curves throughout the whole operating range. A computational fluid dynamics (CFD) model was developed to establish these throttle-closing and throttle-opening performance curves. The flow conditions obtained with the CFD simulations confirm that the hydraulic behavior of the SSCP is influenced by the partial circumferential stall that occurs in the impeller-stator flow channels. It was shown that the inflow conditions to the impeller-stator assembly considerably influence the flow rate of the stall cessation, the size of the hysteresis, and the head generated during part-load operations.
Development of Monocytes, Macrophages, and Dendritic Cells
Authors: Geissmann Frederic , Manz Markus G. , Jung Steffen , Sieweke Michael H. , Merad Miriam , Ley Klaus
Published: February 2010

Development of Myeloid Immune Cells

As leukocytes develop to maturity, they proceed through an array of phenotypically distinct intermediates. For T and B lymphocyte populations, the different developmental stages, anatomical locations, and cell signals required for progression are well established. However, until recently, much less has been known about how development proceeds in the myeloid lineage, which includes monocytes, macrophages, and dendritic cells.

Geissmann
et al.

(p.
656
) review our current understanding of myeloid lineage development and describe the developmental pathways and cues that drive differentiation.
Response to Comment on “Unexpected Epoxide Formation in the Gas-Phase Photooxidation of Isoprene”
Authors: Paulot Fabien , Crounse John D. , Kjaergaard Henrik G. , Kürten Andreas , St. Clair Jason M. , Seinfeld John H. , Wennberg Paul O.
Published: February 2010

Claeys questions whether gaseous epoxydiol is formed from the oxidation of isoprene and whether it is relevant to the formation of isoprene-derived secondary organic aerosol (iSOA). We argue that the alternative mechanism she proposes for iSOA applies primarily to chamber studies with high isoprene and is not as important in the atmosphere, where isoprene concentrations are much lower.
A Coherent Beam Splitter for Electronic Spin States
Authors: Petta J. R. , Lu H. , Gossard A. C.
Published: February 2010

Splitting Quantum States

The ability to manipulate the spin and charge states in quantum dots electrically make them attractive as the building blocks (qubits) for quantum information processing systems.

Petta
et al.

(p.
669
; see the Perspective by

Burkard

) now show that the avoided crossing of a spin-singlet state and spin-triplet state of a double quantum dot can operate as a state splitter. By controlling the rate at which an incoming state is swept across the crossing region, it can be separated into either the singlet or triplet states. The ability to manipulate the quantum states without needing high or local magnetic fields should prove useful in integrated quantum circuits.
100-GHz Transistors from Wafer-Scale Epitaxial Graphene
Authors: Lin Y.-M. , Dimitrakopoulos C. , Jenkins K. A. , Farmer D. B. , Chiu H.-Y. , Grill A. , Avouris Ph.
Published: February 2010

The maximum switching frequency of these devices exceeds that of silicon transistors with similar gate-electrode dimensions.
An Ensemble View of Allostery
Authors: Hilser Vincent J.
Published: February 2010

Proteins existing as ensembles of conformations may be key to understanding signal transduction processes.
Big Battle Brewing Over Elephants at Upcoming CITES Meeting
Authors: Stokstad Erik
Published: February 2010

Wildlife advocates and scientists are concerned that a proposed sale of elephant tusks may spur even more poaching of the animals in Africa.
'Toadness' a Key Feature for Global Spread of These Amphibians
Authors: Pennisi Elizabeth
Published: February 2010

On page
679
of this week's issue of
Science
, researchers reveal what enabled some toads to leave South America, where the first toads originated, for places far afield.
The Long Battle Against a Horrific Disease
Authors: Roberts Leslie
Published: February 2010

When the earthquake devastated Port-au-Prince and the surrounding area on 12 January, a long-running program to combat lymphatic filariasis was gearing up for a major assault on this devastating disease.
Lack of a Clinically Relevant Effect of an Antacid on the Pharmacokinetics of Lersivirine
Authors: Vourvahis M. , Banerjee S. , LaBadie R. , Gore D. , Mayer H.
Published: February 2010

Lersivirine (UK-453,061) is a next-generation nonnucleoside reverse transcriptase inhibitor that displays potent antiviral activity. Lersivirine solubility is pH dependent; therefore, the effect of coadministration of antacid on the pharmacokinetics of lersivirine in healthy subjects was investigated. The ratio of adjusted geometric means (750 mg lersivirine plus 20 ml Maalox Max/750 mg lersivirine alone) for the area under the curve from time zero extrapolated to infinite time (AUC
inf
) was 101.86%, showing that coadministration of an antacid had no effect on lersivirine exposure. Coadministration appeared to be safe and relatively well tolerated.
Empiric Combination Antibiotic Therapy Is Associated with Improved Outcome against Sepsis Due to Gram-Negative Bacteria: a Retrospective Analysis
Authors: Micek Scott T. , Welch Emily C. , Khan Junaid , Pervez Mubashir , Doherty Joshua A. , Reichley Richard M. , Kollef Marin H.
Published: February 2010

The optimal approach for empirical antibiotic therapy in patients with severe sepsis and septic shock remains controversial. A retrospective cohort study was conducted in the intensive care units of a university hospital. The data from 760 patients with severe sepsis or septic shock associated with Gram-negative bacteremia was analyzed. Among this cohort, 238 (31.3%) patients received inappropriate initial antimicrobial therapy (IIAT). The hospital mortality rate was statistically greater among patients receiving IIAT compared to those initially treated with an appropriate antibiotic regimen (51.7% versus 36.4%;
P
< 0.001). Patients treated with an empirical combination antibiotic regimen directed against Gram-negative bacteria (i.e., β-lactam plus aminoglycoside or fluoroquinolone) were less likely to receive IIAT compared to monotherapy (22.2% versus 36.0%;
P
< 0.001). The addition of an aminoglycoside to a carbapenem would have increased appropriate initial therapy from 89.7 to 94.2%. Similarly, the addition of an aminoglycoside would have increased the appropriate initial therapy for cefepime (83.4 to 89.9%) and piperacillin-tazobactam (79.6 to 91.4%). Logistic regression analysis identified IIAT (adjusted odds ratio [AOR], 2.30; 95% confidence interval [CI] = 1.89 to 2.80) and increasing Apache II scores (1-point increments) (AOR, 1.11; 95% CI = 1.09 to 1.13) as independent predictors for hospital mortality. In conclusion, combination empirical antimicrobial therapy directed against Gram-negative bacteria was associated with greater initial appropriate therapy compared to monotherapy in patients with severe sepsis and septic shock. Our experience suggests that aminoglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection.
Fast Standardized Therapeutic-Efficacy Assay for Drug Discovery against Tuberculosis
Authors: Rullas Joaquín , García Juan Ignacio , Beltrán Manuela , Cardona Pere-Joan , Cáceres Neus , García-Bustos José Francisco , Angulo-Barturen Iñigo
Published: February 2010

Murine models of
M
ycobacterium
tuberculosis
infection are essential tools in drug discovery. Here we describe a fast standardized 9-day acute assay intended to measure the efficacy of drugs against
M. tuberculosis
growing in the lungs of immunocompetent mice. This assay is highly reproducible, allows good throughput, and was validated for drug lead optimization using isoniazid, rifampin, ethambutol, pyrazinamide, linezolid, and moxifloxacin.
Kinetic Parameters of Efflux of Penicillins by the Multidrug Efflux Transporter AcrAB-TolC of
Escherichia coli
Authors: Lim Siew Ping , Nikaido Hiroshi
Published: February 2010

The multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including β-lactams. However, the kinetic constants of the efflux process, needed for the quantitative understanding of resistance, were not available until those accompanying the efflux of some cephalosporins were recently determined by combining efflux with the hydrolysis of drugs by the periplasmic β-lactamase. In the present study we extended this approach to the study of a wide range of penicillins, from ampicillin and penicillin V to ureidopenicillins and isoxazolylpenicillins, by combining efflux with hydrolysis with the OXA-7 penicillinase. We found that the penicillins had a much stronger apparent affinity to AcrB and higher maximum rates of efflux than the cephalosporins. All penicillins showed strong positive cooperativity kinetics for export. The kinetic constants obtained were validated, as the MICs theoretically predicted on the basis of efflux and hydrolysis kinetics were remarkably similar to the observed MICs (except for the isoxazolylpenicillins). Surprisingly, however, the efflux kinetics of cloxacillin, for example, whose MIC decreased 512-fold in
Escherichia coli
upon the genetic deletion of the
acrB
gene, were quite similar to those of ampicillin, whose MIC decreased only 2-fold with the same treatment. Analysis of this phenomenon showed that the extensive decrease in the MIC for the
acrB
mutant is primarily due to the low permeation of the drug and that comparison of the MICs between the parent and the
acrB
strains is a very poor measure of the ability of AcrB to pump a drug out.
Leptospiral Endostatin-Like Protein A Is a Bacterial Cell Surface Receptor for Human Plasminogen
Authors: Verma Ashutosh , Brissette Catherine A. , Bowman Amy A. , Shah Samir T. , Zipfel Peter F. , Stevenson Brian
Published: February 2010

The spirochete
Leptospira interrogans
is a highly invasive pathogen of worldwide public health importance. Studies from our laboratories and another have demonstrated that
L. interrogans
can acquire host plasminogen on its surface. Exogenous plasminogen activators can then convert bound plasminogen into the functionally active protease plasmin. In this study, we extend upon those observations and report that leptospiral endostatin-like protein A (LenA) binds human plasminogen in a dose-dependent manner. LenA-plasminogen interactions were significantly inhibited by the lysine analog ξ-aminocaproic acid, suggesting that the lysine-binding sites on the amino-terminal kringle portion of the plasminogen molecule play a role in the binding. Previous studies have shown that LenA also binds complement regulator factor H and the extracellular matrix component laminin. Plasminogen competed with both factor H and laminin for binding to LenA, which suggests overlapping ligand-binding sites on the bacterial receptor. Finally, LenA-bound plasminogen could be converted to plasmin, which in turn degraded fibrinogen, suggesting that acquisition of host-derived plasmin by LenA may aid bacterial dissemination throughout host tissues.
Interaction of
Francisella asiatica
with Tilapia (
Oreochromis niloticus
) Innate Immunity
Authors: Soto Esteban , Fernandez Denise , Thune Ronald , Hawke John P.
Published: February 2010

Members of the genus
Francisella
are facultative intracellular bacteria that cause important diseases in a wide variety of animals worldwide, including humans and fish. Several genes that are important for intramacrophage survival have been identified, including the
iglC
gene, which is found in the
iglABCD
operon in the
Francisella
sp. pathogenicity island (FPI). In the present study, we examined the interaction of wild-type
Francisella asiatica
and a Δ
iglC
mutant strain with fish serum and head kidney-derived macrophages (HKDM). Both the wild-type and the mutant strains were resistant to killing by normal and heat-inactivated sera. The wild-type
F. asiatica
is able to invade tilapia head kidney-derived macrophages and replicate vigorously within them, causing apoptosis and cytotoxicity in the macrophages at 24 and 36 h postinfection. The Δ
iglC
mutant, however, is defective for survival, replication, and the ability to cause cytotoxicity in HKDM, but the ability is restored when the mutant is complemented with the
iglC
gene. Uptake by the HKDM was mediated partially by complement and partially by macrophage mannose receptors, as demonstrated by
in vitro
assays. Light and electron microscopy analysis of the infected macrophages revealed intracellular bacteria present in a tight vacuole at 2 h postinoculation and the presence of numerous bacteria in spacious vacuoles at 12 h postinfection, with some bacteria free in the cytoplasm.