bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional brain imaging in glucocerebrosidase mutation carriers with and without Parkinsonism
Authors: Kono Satoshi , Ouchi Yasuomi , Terada Tatsuhiro , Ida Hiroyuki , Suzuki Makiko , Miyajima Hiroaki
Published: July 2010

Mutations in the glucocerebrosidase gene (GBA) increase the risk for Parkinson's disease and are also associated with an earlier onset of the disease and an akinetic parkinsonian phenotype. To investigate the underlying pathogenesis of this condition, we assessed cerebral metabolism using positron emission tomography (PET) in GBA mutation carriers with and without parkinsonism. [18F]‐fluorodeoxyglucose (FDG)‐PET using a three‐dimensional stereotactic surface projection analysis was used to measure the cerebral metabolic rates of glucose (CMRGlc) in a patient with parkinsonism and Gaucher disease (GD) and five subjects with a heterozygous GBA mutation, including three patients with parkinsonism and three asymptomatic carriers in comparison to 10 healthy controls in the same age range. Dopaminergic neuronal activity was investigated using [11C] CFT‐ and [11C] raclopride‐PET. All GBA mutation carriers displayed a significant CMRGlc decrease in the supplemental motor area (SMA). The carriers with parkinsonism showed additional hypometabolism in the parietooccipital cortices. The CFT and raclopride PET images in the asymptomatic carriers demonstrated the CFT binding to be within normal values in the putamen and a significant increase was observed in the caudate nucleus while raclopride binding in the striatum was in the normal range. An advanced parkinsonian carrier showed decreased CFT binding and increased raclopride binding in the striatum. The decreased CMRGlc in the SMA was characteristic of the GBA mutation carriers. The hypometabolism in the SMA may, therefore, be involved in the clinical characteristics of parkinsonism associated with GBA mutations when the carriers manifest parkinsonism. © 2010 Movement Disorder Society
Use of a reference tissue and blood vessel to measure the arterial input function in DCEMRI
Authors: Fan Xiaobing , Haney Chad R. , Mustafi Devkumar , Yang Cheng , Zamora Marta , Markiewicz Erica J. , Karczmar Gregory S.
Published: July 2010

Accurate measurement of the arterial input function is critical for quantitative evaluation of dynamic contrast enhanced magnetic resonance imaging data. Use of the reference tissue method to derive a local arterial input function avoided large errors associated with direct arterial measurements, but relied on literature values for Ktrans and ve. We demonstrate that accurate values of Ktrans and ve in a reference tissue can be measured by comparing contrast media concentration in a reference tissue to plasma concentrations measured directly in a local artery after the 1–2 passes of the contrast media bolus—when plasma concentration is low and can be measured accurately. The values of Ktrans and ve calculated for the reference tissue can then be used to derive a more complete arterial input function including the first pass of the contrast bolus. This new approach was demonstrated using dynamic contrast enhanced magnetic resonance imaging data from rodent hind limb. Values obtained for Ktrans and ve in muscle, and the shape and amplitude of the derived arterial input function are consistent with published results. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
RF coil considerations for short‐T2 MRI
Authors: Horch R. Adam , Wilkens Ken , Gochberg Daniel F. , Does Mark D.
Published: July 2010

With continuing hardware and pulse sequence advancements, modern MRI is gaining sensitivity to signals from short‐T2 1H species under practical experimental conditions. However, conventional MRI coils are typically not designed for this type of application, as they often contain proton‐rich construction materials that may contribute confounding 1H background signal during short‐T2 measurements. An example of this is shown herein. Separately, a loop‐gap style coil was used to compare different coil construction materials and configurations with respect to observed 1H background signal sizes in a small animal imaging system. Background signal sources were spatially identified and quantified in a number of different coil configurations. It was found that the type and placement of structural coil materials around the loop‐gap resonator, as well as the coil's shielding configuration, are critical determinants of the coil's background signal size. Although this study employed a loop‐gap resonator design, these findings are directly relevant to standard volume coils commonly used for MRI. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
An in vivo verification of the intravoxel incoherent motion effect in diffusion‐weighted imaging of the abdomen
Authors: Lemke Andreas , Laun Frederik B. , Simon Dirk , Stieltjes Bram , Schad Lothar R.
Published: July 2010

To investigate the vascular contribution to the measured apparent diffusion coefficient and to validate the Intra Voxel Incoherent Motion theory, the signal as a function of the b‐value was measured in the healthy pancreas with and without suppression of the vascular component and under varying echo times (TE = 50, 70, and 100 msec). The perfusion fraction f and the diffusion coefficient D were extracted from the measured DW‐data using the original Intra Voxel Incoherent Motion‐equation and a modified version of this equation incorporating relaxation effects. First, the perfusion fraction f in the blood suppressed pancreatic tissue decreased significantly (P = 0.03), whereas the diffusion coefficient D did not change with suppression (P = 0.43). Second, the perfusion fraction f increased significantly with increasing echo time (P = 0.0025), whereas the relaxation time compensated perfusion fraction f′ showed no significant dependence on TE (P = 0.31). These results verify a vascular contribution to the diffusion weighted imaging measurement at low b values and support the Intra Voxel Incoherent Motion‐theory. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Challenges towards MR imaging of the peripheral inflammatory response in the subacute and chronic stages of transient focal ischemia
Authors: Farr Tracy D. , Seehafer Jörg U. , Nelles Melanie , Hoehn Mathias
Published: July 2010

Intravenous administration of iron oxide nanoparticles after experimental stroke has been shown to produce focal signal intensity changes in the ischemic boundary on MRI images. These changes have been attributed to the influx of iron‐laden blood‐borne macrophages, although it has been suggested that this effect might not always be completely specific to inflammatory cells. The aim of the present study was to investigate this phenomenon in a subacute time frame that is more relevant to the peripheral inflammatory response. Imaging experiments (T2‐, T2*‐ and T1‐weighted sequences) were acquired in Wistar rats 6 days after transient middle cerebral artery occlusion (MCAO). Animals were intravenously infused with different doses of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (300, 600 or 1000 µmol Fe/kg), or saline and gadolinium, and imaged again 24 h later. Tissue was immediately processed for immunohistochemistry with the macrophage marker ED‐1, in combination with Prussian blue for iron. Ischemic tissue exhibited a large increase in T2 values, and overall contrast enhancement was apparent in the brain and surrounding muscle. In contrast with previous reports, there were no regions of focal signal intensity changes in the ischemic territory in any of the images, although a region of interest analysis revealed a trend towards iron accumulation in the ischemic hemisphere, particularly in the cortex of T2* images. However, histological examination revealed that, despite extensive ED‐1‐positive macrophage accumulation in the entire ischemic territory, none of these cells were Prussian blue positive, except in the meninges of one animal that received a high dose of USPIO nanoparticles. These results imply that the observed trend is a result of the presence of contrast agent in the blood, or meninges, and not iron‐containing inflammatory cells. Copyright © 2010 John Wiley & Sons, Ltd.
Changes in the proteome and phosphoproteome expression in the bryozoan Bugula neritina larvae in response to the antifouling agent butenolide
Authors: Qian Pei‐Yuan , Wong Yue Him , Zhang Yu
Published: July 2010

Larval attachment and metamorphosis, commonly referred to as larval settlement, of marine sessile invertebrates can be triggered or blocked by chemical cues and affected by changes in overall protein expression pattern and phosphorylation dynamics. This study focuses on the effects of butenolide, an effective larval settlement inhibitor, on larval settlement at the proteome level in the bryozoan Bugula neritina. Liquid‐phase IEF sample prefractionation combined with 2‐DE and MALDI‐TOF MS was used to identify the differentially expressed proteins. Substantial changes occurred both in protein abundance and in phosphorylation status during larval settlement and when settling larvae were challenged with butenolide. The proteins that responded to treatment were identified as structural proteins, molecular chaperones, mitochondrial peptidases and calcium‐binding proteins. Compared with our earlier results, both genistein and butenolide inhibited larval settlement of B. neritina primarily by changes in protein abundance and the phosphorylation status of proteins but have different protein targets in the same species. Clearly, to design potent antifouling compounds and to understand the mode of action of compounds, more studies on the effects of different compounds on proteome and phosphoproteome of different larval species are required.
JAK2/STAT5 signaling pathway mediates Bojungbangdocktang enhanced hematopoiesis
Authors: Lim Jeonghan , Jeong Soo‐Jin , Koh Wonil , Han Ihn , Lee Hyo‐Jung , Kwon Tae‐Rin , Jung Ji Hoon , Kim Jung Hyo , Lee Hyo‐Jeong , Lee Eun‐Ok , Kim Sun‐Hyung , Lee Min‐Ho , Kim Sung‐Hoon
Published: July 2010

Bojungbangdocktang (BJBDT) is a medicinal herbal cocktail that has been used for cancer prevention and treatment in traditional Korean medicine. In the current study, BJBDT was demonstrated to regulate hematopoiesis. BJBDT significantly increased the expression of hematopoietic cytokines interleukin (IL)‐3, stem cell factor (SCF), granulocyte‐macrophage‐colony stimulating factor (GM‐CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in hematopoietic stem cells (HSCs). Additionally, BJBDT enhanced the phosphorylation of Janus activated kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) and STAT binding to gamma interferon activated sites (GAS) in HSCs. Furthermore, BJBDT significantly enhanced the growth rate of granulocyte erythrocyte monocyte macrophage colony‐forming units (CFU‐GEMM) and erythroid burst forming units (BFU‐E) in vitro. Moreover, BJBDT increased the level of EPO at mRNA in kidney and plasma, and the numbers of erythroid‐specific antigen Ter‐119+ erythroid cells in mice with aplastic anemia induced by 20% benzene. Consistently, histochemical staining revealed BJBDT increased the bone marrow and stromal cells as well as decreased macrophages and adipocytes in bone marrow tissues of mice with aplastic anemia. Taken together, the results suggest that BJBDT can enhance hematopoiesis via hematopoietic cytokine‐mediated JAK2/STAT5 pathway as a potent hematopoietic candidate. Copyright © 2010 John Wiley & Sons, Ltd.
Comment on ‘Estimating average annual per cent change in trend analysis’ by Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK, Statistics in Medicine 2009; 28:3670–3682
Authors: Muggeo Vito M. R.
Published: July 2010

We discuss some issues relevant to paper of Clegg and co‐authors published in Statistics in Medicine; 28, 3670‐3682. Emphasis is on computation of the variance of the sum of products of two estimates, slopes and breakpoints. Copyright © 2010 John Wiley & Sons, Ltd.
Enhancing Surface Plasmon Detection Using Ultrasmall Nanoslits and a Multispectral Integration Method
Authors: Lee Kuang‐Li , Wei Pei‐Kuen
Published: July 2010

A multispectral integration method to increase the detection limit of gold nanostructures is presented. This method considers all the resonances due to localized surface plasmons, Bloch wave surface plasmons, and Wood’s anomalies. By integrating the wavelength shifts together with intensity changes over these resonances, the detection resolution is increased to about six times larger than that of commonly used wavelength or intensity methods. Further studies with different nanostructures show the detection sensitivity is increased with the decrease of aperture size. The detection limit for 40‐nm nanoslits is improved by about seven times relative to that for 300‐nm nanoslits. For sub‐100‐nm apertures, the detection resolution for nanoslits is better than that for nanoholes due to its non‐cutoff transmission. The advantage of using the multispectral integration method in biosensing is verified by antigen–antibody interaction experiments.
Aesthetic principles and cognitive emotion appraisals: How much of the beauty lies in the eye of the beholder?
Authors: Kumar Minu , Garg Nitika
Published: July 2010

Although the aesthetic properties of a product have often been linked to consumers’ emotional responses, theory and empirical evidence are yet to fully explain how and why aesthetic properties of a product evoke an emotional response. Drawing on an eclectic literature, we propose hypotheses connecting aesthetic principles with the subconscious cognitive appraisals associated with emotions. Specifically, we empirically test the relationships between the aesthetic principle of harmony and cognitive appraisals (attentional activity and pleasantness), while exploring the moderating role of typicality. Our results suggest that harmony and typicality interact to affect appraisals of pleasantness and attentional activity. Specifically, consumers tend to prefer designs that balance the levels of attentional resources needed and pleasantness in visually evaluating the design. This work advances the growing literature in product design and aesthetics by providing an understanding of the mechanisms through which aesthetic principles might prompt emotional responses in consumers.
“The World the Horses Made”: A South African Case Study of Writing Animals into Social History
Authors: Swart Sandra
Published: July 2010

This paper explores new ways to write history that engages with the lives of animals. It offers a sample card of how social history can be enriched by focusing on history from an animal perspective – and equally, how the tools provided by social history reveals the historicity of animals. The case study is drawn from South African history and the focus is on horses. The paper firstly proposes that horses changed human history not only on the macro-level, but in the small, intimate arena of the bodily, following Febvre’s call for a sensory history. Secondly, this paper explores social history’s long-time concern with agency and with understanding socio-cultural experiences from the perspective of those who actually lived them – in this case, from an equine perspective. Thirdly, the paper asks how social history that takes animals seriously might be written and might offer a fresh dimension to our understanding, with examples from the most analysed event in southern African historiography, the South African War (1899–1902).
Cetacean distribution and relative abundance in offshore Gabonese waters
Authors: de Boer Marijke N.
Published: July 2010

Information on cetaceans off Gabon in tropical West Africa is summarized from boat-based surveys carried out between 7 March and 7 August 2009. Thirteen cetacean species were positively identified comprising two baleen whale species, one sperm whale species and ten species of delphinid. Bryde's whale (Balaenoptera brydei) and humpback whale (Megaptera novaeangliae) were the most frequently encountered species. Cetaceans were found throughout a range of sea surface temperature between 20.5°C and 27.5°C and a wide range of depths with the majority of effort and sightings occurring seaward of the shelf break. Of particular interest from the study were the following: (1) Gabonese waters have a broad cetacean diversity, especially with a large and diversified delphinid community in the northern part of the study area; (2) the variations in oceanographic conditions within Gabonese waters are likely to result in a temporal variation in species composition; (3) the sightings of Atlantic spotted dolphin (Stenella frontalis) are the first at-sea sightings confirmed for these waters, although not unexpected given their distribution and abundant presence in surrounding waters; and (4) the poorly known Clymene dolphin (Stenella clymene) was sighted on four occasions in deep oceanic waters and was the most abundant cetacean. These are the first confirmed records of Clymene dolphins in Gabonese waters.
The nutritional adequacy of plant-based diets
Authors: Sanders T. A. B.
Published: July 2010

The nutritional adequacy of plant-based diets is discussed. Energy and protein intakes are similar for plant-based diets compared with those containing meat. Fe and vitamin B12are the nutrients most likely to be found lacking in such diets. Bioactive substances present in foods of plant origin significantly influence the bioavailability of minerals and requirements for vitamins. Well-balanced vegetarian diets are able to support normal growth and development. It is concluded that meat is an optional rather than an essential constituent of human diets.
Imaging Upregulated Brain Arachidonic Acid Metabolism in HIV-1 Transgenic Rats
Authors: Basselin Mireille , Ramadan Epolia , Igarashi Miki , Chang Lisa , Chen Mei , Kraft Andrew D , Harry G Jean , Rapoport Stanley I
Published: July 2010

Human immunodeficiency virus (HIV)-associated infection involves the entry of virus-bearing monocytes into the brain, followed by microglial activation, neuroinflammation, and upregulated arachidonic acid (AA) metabolism. The HIV-1 transgenic (Tg) rat, a noninfectious HIV-1 model, shows neurologic and behavioral abnormalities after 5 months of age. We hypothesized that brain AA metabolism would be elevated in older HIV-1 Tg rats in vivo. Arachidonic acid incorporation from the plasma into the brain of unanesthetized 7-to-9-month-old rats was imaged using quantitative autoradiography, after [1-14C]AA infusion. Brain phospholipase (PLA2) activities and eicosanoid concentrations were measured, and enzymes were localized by immunostaining. AA incorporation coefficients k* and rates Jin, measures of AA metabolism, were significantly higher in 69 of 81 brain regions in HIV-1 Tg than in control rats, as were activities of cytosolic (c)PLA2-IV, secretory (s)PLA2, and calcium independent (i)PLA2-VI, as well as prostaglandin E2 and leukotriene B4 concentrations. Immunostaining of somatosensory cortex showed elevated cPLA2-IV, sPLA2-IIA, and cyclooxygenase-2 in neurons. Brain AA incorporation and other markers of AA metabolism are upregulated in HIV-1 Tg rats, in which neurologic changes and neuroinflammation have been reported. Positron emission tomography with [1-11C]AA could be used to test whether brain AA metabolism is upregulated in HIV-1-infected patients, in relation to cognitive and behavioral disturbances.
Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling
Authors: Elgebaly Mostafa M , Prakash Roshini , Li Weiguo , Ogbi Safia , Johnson Maribeth H , Mezzetti Erin M , Fagan Susan C , Ergul Adviye
Published: July 2010

Temporary focal ischemia causes greater hemorrhagic transformation (HT) in diabetic Goto-Kakizaki (GK) rats, a model with increased cerebrovascular matrix metalloprotease (MMP) activity and tortuosity. The objective of the current study was to test the hypotheses that (1) diabetes-induced cerebrovascular remodeling is MMP dependent and (2) prevention of vascular remodeling by glucose control or MMP inhibition reduces HT in diabetic stroke. Control and GK rats were treated with vehicle, metformin, or minocycline for 4 weeks, and indices of remodeling including vascular tortuosity index, lumen diameter, number of collaterals, and middle cerebral artery (MCA) MMP activity were measured. Additional animals were subjected to 3 hours MCA occlusion/21 hours reperfusion, and infarct size and HT were evaluated as indices of neurovascular injury. All remodeling markers including MMP-9 activity were increased in diabetes. Infarct size was smaller in minocycline-treated animals. Both metformin and minocycline reduced vascular remodeling and severity of HT in diabetes. These results provide evidence that diabetes-mediated stimulation of MMP-9 activity promotes cerebrovascular remodeling, which contributes to greater HT in diabetes. Metformin and minocycline offer vascular protection, which has important clinical implications for diabetes patients who are at a fourfold to sixfold higher risk for stroke.
Role of a PA14 domain in determining substrate specificity of a glycoside hydrolase family 3 β-glucosidase from Kluyveromyces marxianus
Authors: Yoshida Erina , Hidaka Masafumi , Fushinobu Shinya , Koyanagi Takashi , Minami Hiromichi , Tamaki Hisanori , Kitaoka Motomitsu , Katayama Takane , Kumagai Hidehiko
Published: July 2010

β-Glucosidase from Kluyveromyces marxianus (KmBglI) belongs to the GH3 (glycoside hydrolase family 3). The enzyme is particularly unusual in that a PA14 domain (pf07691), for which a carbohydrate-binding role has been claimed, is inserted into the catalytic core sequence. In the present study, we determined the enzymatic properties and crystal structure of KmBglI in complex with glucose at a 2.55 Å (1 Å=0.1 nm) resolution. A striking characteristic of KmBglI was that the enzyme activity is essentially limited to disaccharides, and when trisaccharides were used as the substrates the activity was drastically decreased. This chain-length specificity is in sharp contrast with the preferred action on oligosaccharides of barley β-D-glucan glucohydrolase (ExoI), which does not have a PA14 domain insertion. The structure of subsite (−1) of KmBglI is almost identical with that of Thermotoga neapolitana β-glucosidase and is also similar to that of ExoI, however, the structures of subsite (+1) significantly differ among them. In KmBglI, the loops extending from the PA14 domain cover the catalytic pocket to form subsite (+1), and hence simultaneously become a steric hindrance that could limit the chain length of the substrates to be accommodated. Mutational studies demonstrated the critical role of the loop regions in determining the substrate specificity. The active-site formation mediated by the PA14 domain of KmBglI invokes α-complementation of β-galactosidase exerted by its N-terminal domain, to which the PA14 domain shows structural resemblance. The present study is the first which reveals the structural basis of the interaction between the PA14 domain and a carbohydrate.
Properties of knotted ring polymers. I. Equilibrium dimensions
Authors: Mansfield Marc L. , Douglas Jack F.
Published: July 2010

We report calculations on three classes of knotted ring polymers: (1) simple-cubic lattice self-avoiding rings (SARs), (2) “true” theta-state rings, i.e., SARs generated on the simple-cubic lattice with an attractive nearest-neighbor contact potential (θ-SARs), and (3) ideal, Gaussian rings. Extrapolations to large polymerization index N imply knot localization in all three classes of chains. Extrapolations of our data are also consistent with conjectures found in the literature which state that (1) Rg→ANν asymptotically for ensembles of random knots restricted to any particular knot state, including the unknot; (2) A is universal across knot types for any given class of flexible chains; and (3) ν is equal to the standard self-avoiding walk (SAW) exponent (≅0.588) for all three classes of chains (SARs, θ-SARs, and ideal rings). However, current computer technology is inadequate to directly sample the asymptotic domain, so that we remain in a crossover scaling regime for all accessible values of N. We also observe that Rg∼p−0.27, where p is the “rope length” of the maximally inflated knot. This scaling relation holds in the crossover regime, but we argue that it is unlikely to extend into the asymptotic scaling regime where knots become localized.
Deep levels induced by reactive ion etching in n- and p-type 4H–SiC
Authors: Kawahara Koutarou , Krieger Michael , Suda Jun , Kimoto Tsunenobu
Published: July 2010

In this study, the authors investigate deep levels, which are induced by reactive ion etching (RIE) of n-type/p-type 4H–SiC, by deep level transient spectroscopy (DLTS). The capacitance of a Schottky contact fabricated on as-etched p-type SiC is abnormally small due to compensation or deactivation of acceptors extending to a depth of ∼14 μm, which is nearly equal to the epilayer thickness. The value of the capacitance can recover to that of a Schottky contact on as-grown samples after annealing at 1000 °C. However, various kinds of defects, IN2 (EC−0.30 eV), EN (EC−1.6 eV), IP1 (EV+0.30 eV), IP2 (EV+0.39 eV), IP4 (HK0: EV+0.72 eV), IP5 (EV+0.85 eV), IP7 (EV+1.3 eV), and EP (EV+1.4 eV), remain at a high concentration (average of total defect concentration in the region ranging from 0.3 μm to 1.0 μm:∼5×1014 cm−3) even after annealing at 1000 °C. The concentration of all these defects generated by RIE, except for the IP4 (HK0) center, remarkably decreases by thermal oxidation. In addition, the HK0 center can also be reduced significantly by a subsequent annealing at 1400 °C in Ar.
Diarrhoea during enteral nutrition is predicted by the poorly absorbed short‐chain carbohydrate (FODMAP) content of the formula
Authors: Halmos E. P. , Muir J. G. , Barrett J. S. , Deng M. , Shepherd S. J. , Gibson P. R.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 925–933

Background  Although it is recognized that diarrhoea commonly complicates enteral nutrition, the causes remain unknown.

Aim  To identify factors associated with diarrhoea in patients receiving enteral nutrition with specific attention to formula composition.

Methods  Medical histories of in‐patients receiving enteral nutrition were identified by ICD‐10‐AM coding and randomly selected from the year 2003 to 2008. Clinical and demographic data were extracted. Formulas were classified according to osmolality, fibre and FODMAP (fermentable oligo‐, di‐ and mono‐saccharides and polyols) content.

Results  Formula FODMAP levels ranged from 10.6 to 36.5 g/day. Of 160 patients receiving enteral nutrition, 61% had diarrhoea. Univariate analysis showed diarrhoea was associated with length of stay >21 days (OR 4.2), enteral nutrition duration >11 days (OR 4.0) and antibiotic use (OR 2.1). After adjusting for influencing variables through a logistic regression model, a greater than five‐fold reduction in risk of developing diarrhoea was seen in patients initiated on Isosource 1.5 (P = 0.029; estimated OR 0.18). The only characteristic unique to this formula was its FODMAP content, being 47–71% lower than any other formula.

Conclusions  Length of stay and enteral nutrition duration independently predicted diarrhoea development, while being initiated on a lower FODMAP formula reduced the likelihood of diarrhoea. As retrospective evaluation does not support a cause–effect relationship, an interventional study investigating FODMAPs in enteral formula is indicated.
Influence of hepatic impairment on pharmacokinetics of the human GLP‐1 analogue, liraglutide
Authors: Flint Anne , Nazzal Khalil , Jagielski Pawel , Hindsberger Charlotte , Zdravkovic Milan
Published: July 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Liraglutide is a novel human GLP‐1 analogue approved for treatment of type 2 diabetes mellitus. Since there is a high prevalence of co‐morbid hepatic impairment in this population it is of clinical importance to establish whether the pharmacokinetics of liraglutide are affected by hepatic impairment.

WHAT THIS STUDY ADDS

• This study shows that hepatic impairment does not increase liraglutide exposure. Rather, total exposure tends to decrease with increasing degree of hepatic impairment.

AIMS

To compare the pharmacokinetics (PK) of a single‐dose of liraglutide in subjects with hepatic impairment.

METHODS

This parallel group, open label trial involved four groups of six subjects with healthy, mild, moderate and severe hepatic impairment, respectively. Each subject received 0.75 mg of liraglutide (s.c., thigh), and blood samples were taken over 72 h for PK assessment. Standard laboratory and safety data were collected. The primary endpoint was area under the plasma liraglutide concentration–time curve from time zero to infinity (AUC(0,∞)).

RESULTS

Exposure to liraglutide was not increased by hepatic impairment. On the contrary, mean AUC(0,∞) was highest for healthy subjects and lowest for subjects with severe hepatic impairment (severe/healthy: 0.56, with 90% CI 0.39, 0.81) and equivalence in this parameter across groups was not demonstrated. Cmax also tended to decrease with hepatic impairment (severe/healthy: 0.71, with 90% CI 0.52, 0.97), but tmax was similar across groups (11.3–13.2 h). There were no serious adverse events, hypoglycaemic episodes or clinically significant changes in laboratory parameters and liraglutide was considered well tolerated.

CONCLUSIONS

This study indicated no safety concerns regarding use of liraglutide in patients with hepatic impairment. Exposure to liraglutide was not increased by impaired liver function; rather, the results suggest a decreased exposure with increasing degree of hepatic impairment. However, data are not conclusive to suggest a dose increase of liraglutide. Thus, the results indicate that patients with type 2 diabetes mellitus and hepatic impairment can use standard treatment regimens of liraglutide. There is, however, currently limited clinical experience with liraglutide in patients with hepatic impairment.
Guild‐specific patterns of species richness and host specialization in plant–herbivore food webs from a tropical forest
Authors: Novotny Vojtech , Miller Scott E. , Baje Leontine , Balagawi Solomon , Basset Yves , Cizek Lukas , Craft Kathleen J. , Dem Francesca , Drew Richard A. I. , Hulcr Jiri , Leps Jan , Lewis Owen T. , Pokon Rapo , Stewart Alan J. A. , Allan Samuelson G. , Weiblen George D.
Published: July 2010

1. The extent to which plant–herbivore feeding interactions are specialized is key to understand the processes maintaining the diversity of both tropical forest plants and their insect herbivores. However, studies documenting the full complexity of tropical plant–herbivore food webs are lacking.

2. We describe a complex, species‐rich plant–herbivore food web for lowland rain forest in Papua New Guinea, resolving 6818 feeding links between 224 plant species and 1490 herbivore species drawn from 11 distinct feeding guilds. By standardizing sampling intensity and the phylogenetic diversity of focal plants, we are able to make the first rigorous and unbiased comparisons of specificity patterns across feeding guilds.

3. Specificity was highly variable among guilds, spanning almost the full range of theoretically possible values from extreme trophic generalization to monophagy.

4. We identify guilds of herbivores that are most likely to influence the composition of tropical forest vegetation through density‐dependent herbivory or apparent competition.

5. We calculate that 251 herbivore species (48 of them unique) are associated with each rain forest tree species in our study site so that the ∼200 tree species coexisting in the lowland rain forest community are involved in ∼50 000 trophic interactions with ∼9600 herbivore species of insects. This is the first estimate of total herbivore and interaction number in a rain forest plant–herbivore food web.

6. A comprehensive classification of insect herbivores into 24 guilds is proposed, providing a framework for comparative analyses across ecosystems and geographical regions.
The Duffy blood groups of Jarawas – the primitive and vanishing tribe of Andaman and Nicobar Islands of India
Authors: Das M. K. , Singh S. S. , Adak T. , Vasantha K. , Mohanty D.
Published: July 2010

summary.  Andaman and Nicobar Islands, union territory of India were inhabited by 14 aboriginal tribes. Some of these tribal populations have already become extinct, and the numbers of the existing ones are also dwindling. This group of islands being highly endemic for malaria, it was considered worthwhile to study the hunter‐gatherer primitive tribe, Jarawas, for their Duffy blood group phenotype.

Jarawas, the primitive tribe of Andaman Islands, inhabit the three jungle areas of South and one jungle area of Middle Andaman. Blood samples of 116 Jarawas were collected and tested for Duffy blood group and malarial parasite infectivity. The Duffy blood grouping was performed as per standard serological techniques, and peripheral smears were screened for malarial parasite and if present parasite density count was performed and the species identified.

The results showed a total absence of both Fya and Fyb antigens in two areas (Kadamtala and R.K. Nallah) and low prevalence of Fya antigen in another two areas (Jirkatang and Tirur). There was absence of malarial parasite Plasmodium vivax infection though Plasmodium falciparum infection was present in 27·59% of cases.

A very high frequency of Fy (a–b–) in the Jarawa tribe from all the four jungle areas of Andaman Islands along with total absence of P. vivax infections suggests the selective advantage offered to Fy (a–b–) individuals against P vivax infection.
Comparison and evaluation of a novel bioassay and high‐performance liquid chromatography for the clinical measurement of serum voriconazole concentrations
Authors: Steinmann Joerg , Huelsewede Joerg , Buer Jan , Rath Peter‐Michael
Published: July 2010

The aim of this study was to develop and validate a novel bioassay for determining serum voriconazole (VRC) concentrations and to compare its routine clinical performance with that of high‐performance liquid chromatography (HPLC). The biological activity of VRC was measured by a plate diffusion assay using a VRC‐hypersusceptible Candida kefyr strain. The bioassay’s utility was tested by measuring steady‐state VRC concentrations in 100 serum probes from VRC‐treated patients. The HPLC system used solvent extraction with hexane : dichloromethane followed by reversed‐phase HPLC with ultraviolet detection. The intra‐day and inter‐day accuracy of the bioassay was <5%, while that of HPLC was <1%. The precision (mean coefficient of variation, 3.5%) was equal for both the methods. The limit of quantification was lower for HPLC (0.2 mg l−1) than for the bioassay (0.5 mg l−1). The result of linear regression analysis was HPLC = 1.0178 (bioassay) + 0.328; R2 = 0.88; n = 100. Results of the serum panel ranged from 0.5 to more than 8.0 mg l−1 for the bioassay and from 0.26 to 10.1 mg l−1 for HPLC. Especially in laboratories without access to HPLC, the bioassay may be a clinically useful tool for therapeutic drug monitoring.
The Effect of Exchange Rates on Firm Exports: The Role of Imported Intermediate Inputs
Authors: Greenaway David , Kneller Richard , Zhang Xufei
Published: July 2010

In this paper we investigate the effect of exchange rate changes on the exports of UK manufacturing firms, but draw on the macro literature to consider the effects exchange rates have on imported intermediate inputs. Real exchange rate appreciations make the foreign export price of goods and services produced by domestic firms more expensive, but also make imported inputs cheaper. Our results provide support for this view; we find a significant negative effect from a measure of the export destination weighted real effective exchange rate and an offsetting effect from the imported intermediate input weighted exchange rate on export sales.
Rufinamide in refractory childhood epileptic encephalopathies other than Lennox–Gastaut syndrome
Authors: Coppola G. , Grosso S. , Franzoni E. , Veggiotti P. , Zamponi N. , Parisi P. , Spalice A. , Habetswallner F. , Fels A. , Verrotti A. , D’Aniello A. , Mangano S. , Balestri A. , Curatolo P. , Pascotto A.
Published: July 2010

Background:  To report on the first multicenter Italian experience with rufinamide as adjunctive drug in children, adolescents and young adults with refractory childhood‐onset epileptic encephalopathies other than Lennox–Gastaut syndrome.

Methods:  Thirty‐eight patients (19 males, 19 females), aged between 4 and 34 (mean 13.7 ± 8.3, median 12.5), all affected by different types of childhood‐onset refractory epileptic encephalopathies other than Lennox–Gastaut syndrome, were treated with rufinamide as adjunctive drug for a mean period of 11.4 months (range 3–26 months).

Results:  Fifteen of 38 patients (39.5%) had a ≥50% seizure reduction in countable seizures. Complete seizure freedom was achieved in one of these patients (2.6%). Three patients (7.9%) had a 25–49% seizure reduction, whilst seizure frequency remained unchanged in 15 (39.5%) and increased in five patients (13.1%). Eleven patients (28.9%) reported adverse side effects. Vomiting was reported in five patients (13.1%); drowsiness, decreased appetite and irritability with migraine manifested in other four patients. They were transient and mild in all cases.

Conclusion:  Rufinamide may be an effective and well‐tolerated adjunctive drug for the treatment of refractory childhood‐onset epileptic encephalopathies other than Lennox–Gastaut syndrome. Rufinamide was most effective in patients with drop‐attacks and (bi)frontal spike–wave discharges.
PPAR activation has dichotomous control on the expression levels of cytosolic and secretory phospholipase A2 in astrocytes; inhibition in naïve, untreated cells and enhancement in LPS‐stimulated cells
Authors: Sergeeva Marina G. , Aleshin Stepan E. , Grabeklis Sevil , Reiser Georg
Published: July 2010

J. Neurochem. (2010) 115, 399–410.

Despite the importance of cytosolic phospholipase A2 type IVA (cPLA2) and secretory PLA2 (sPLA2) in physiological and pathological responses of astrocytes in inflammatory conditions, the regulation of the expression of these genes is still unclear. Both genes have peroxisome proliferator‐activated receptors (PPAR) binding sites in their promoters. The role of synthetic PPAR agonists in the regulation of gene expression in naïve and lipopolysaccharide (LPS)‐stimulated rat astrocytes in culture was investigated. Exposure to LPS resulted in a time‐dependent, fourfold transient increase of sPLA2 expression, with maximum at 4 h; cPLA2 expression was notably increased after 16‐h LPS stimulation. Using selective PPARα, PPARβ/δ, and PPARγ agonists, we found that expression of both cPLA2 and sPLA2 is under PPAR control, but with different isotypes sensitivity. In naïve astrocytes, all three PPAR agonists significantly suppressed the expression of sPLA2, while only PPARα and PPARγ activation suppressed cPLA2 expression. Astonishingly, simultaneous addition of LPS with PPAR agonists evoked the opposite effect. All three PPAR agonists induced potentiation of cPLA2 expression level. Potentiation of sPLA2 expression was induced only by simultaneous addition of LPS with PPARγ agonist. By knockdown of PPARα, PPARβ/δ, and PPARγ, we confirmed the involvement of PPAR‐dependent pathways. The important novelty of our findings is that both sPLA2 and cPLA2 are under dichotomous control of PPARs: suppression in naïve control cells, but induction in LPS‐stimulated astrocytes.
BIODIVERSITY RESEARCH: Parasites of exotic species in invaded areas: does lower diversity mean lower epizootic impact?
Authors: Mastitsky Sergey E. , Karatayev Alexander Y. , Burlakova Lyubov E. , Molloy Daniel P.
Published: July 2010

Aim  Exotic species may serve as vectors for the introduction of parasites from their native range and may also become infected by parasites already present in invaded areas, but the total number of parasites infecting such exotic species in their invaded areas is typically less than that in their native range. We tested whether the diversity of parasites associated with exotic species in the native and invaded areas is related to the epizootic impact these parasites cause.

Location  Global.

Methods  We examined the diversity and epizootic impact of 384 parasite taxa associated with 22 exotic freshwater invertebrate species. The epizootic impact of each parasite was rated based on whether it had been documented to cause a major pathological impact on a large proportion of an infected host population (other than the invader under consideration).

Results  The total number of parasites associated with an exotic host in its native range was about twice that of all parasites associated with it in its entire invaded range. This was mainly because of the loss in the invaded areas of low impact parasites, whereas the average number of high impact parasites per host in these areas did not differ statistically from that in the native range.

Main conclusions  Our study suggests similar levels of adverse impact of parasites of exotic species in both their native and invaded areas. In addition to the introduction of highly pathogenic exotic parasites, other mechanisms that may be involved include (1) acquisition by the invaders of new high impact parasites in the invaded ranges, (2) high abundance of the invaders in their new ranges and (3) susceptibility of novel hosts to exotic parasites because of the ‘naive host syndrome’.
Implications of the proposed Soil Framework Directive on agricultural systems in Atlantic Europe – a review
Authors: Creamer R. E. , Brennan F. , Fenton O. , Healy M. G. , Lalor S. T. J. , Lanigan G. J. , Regan J. T. , Griffiths B. S.
Published: July 2010

The main threats to soils outlined in the pending Soil Framework Directive (SFD) are: contamination, loss of organic matter, erosion, compaction, sealing, salinization and desertification. The first four threats are pertinent to agricultural systems in Atlantic Europe, but vary in their extent between countries depending on the spatial soil distribution. Loss of soil biodiversity has not been included as a potential threat in the SFD due to lack of information that is currently available both spatially and temporally to facilitate any legislation to protect it. This paper gives emphasis to the four main threats outlined above associated with Agricultural systems in Atlantic Europe. Each soil threat is discussed in relation to the agricultural management calendar for cultivated and grazed grassland soils. The paper discusses current soil protection policies and possible changes to such legislation with the adoption of the SFD by member states.
Association of salivary lysozyme and C‐reactive protein with metabolic syndrome
Authors: Qvarnstrom Markku , Janket Sok‐Ja , Jones Judith A. , Jethwani Kamal , Nuutinen Pekka , Garcia Raul I. , Baird Alison E. , Van Dyke Thomas E. , Meurman Jukka H.
Published: July 2010

Qvarnstrom M, Janket S‐J, Jones JA, Jethwani K, Nuutinen P, Garcia RI, Baird AE, Van Dyke TE and Meurman JH. Association of salivary lysozyme and C‐reactive protein with metabolic syndrome. J Clin Periodontol 2010; 37: 805–811. doi: 10.1111/j.1600‐051X.2010.01605.x.

Introduction: Salivary lysozyme (SLZ) is a proteolytic enzyme secreted by oral leucocytes and contains a domain that has an affinity to advanced glycation end products (AGE). Thus, we hypothesized that SLZ would be associated with metabolic syndrome (metS), a pro‐inflammatory state.

Methods: Utilizing cross‐sectional data from 250 coronary artery disease (CAD) and 250 non‐CAD patients, the association of SLZ with metS was tested by logistic regression analyses controlling for age, sex, smoking, total cholesterol and C‐reactive protein (CRP) levels. The analyses were stratified by CAD status to control for the possible effects of CAD.

Results: MetS was found in 122 persons. The adjusted odds ratio (OR) for metS associated with the highest quartile of SLZ was 1.95 with 95% confidence interval (CI) 1.20–3.12, p‐value=0.007, compared with the lower three quartiles combined. Among the 40 subjects with metS but without CAD, the OR was 1.63 (CI: 0.64–4.15, p=0.31), whereas in the CAD group, SLZ was significantly associated with metS [OR=1.96 (1.09–3.52), p=0.02]. In both subgroups, CRP was not significantly associated with metS.

Conclusion: SLZ was significantly associated with metS (OR=1.95) independent of CRP level. Future longitudinal research is warranted.
Infectivity and pathogenicity of canine H3N8 influenza A virus in horses
Authors: Yamanaka Takashi , Tsujimura Koji , Kondo Takashi , Matsumura Tomio , Ishida Hideharu , Kiso Makoto , Hidari Kazuya I. P. J. , Suzuki Takashi
Published: July 2010

Please cite this paper as: Yamanaka et al. (2010) Infectivity and pathogenicity of canine H3N8 influenza A virus in horses. Influenza and Other Respiratory Viruses 4(6), 345–351.

Background  Equine H3N8 influenza A viruses (EIVs) cause respiratory disease in horses and circulate among horses worldwide. In 2004, an outbreak of canine H3N8 influenza A virus (CIV) occurred among dogs in Florida and has spread among dogs in the United States (US). Genetic analyses revealed that this CIV is closely related to the recent EIVs. Although CIV‐infected dogs could be the source of H3N8 influenza A virus for horses, it remains unclear whether the CIV circulating in the United States still maintains its infectivity and/or pathogenicity in horses. To address this, we investigated the infectivity and pathogenicity of CIV in horses and the receptor binding specificity of CIV.

Materials and methods  Three horses were inoculated with A/canine/Colorado/30604/2006 (CO06, H3N8). Clinical signs and nasal swabs were recorded or collected every day. We also evaluated the virus binding to α2‐3‐linked 5‐N‐acetylneuraminic acid (NeuAcα2‐3Gal) and 5‐N‐glycolylneuraminic acid (NeuGcα2‐3Gal) receptor analogues.

Results  Although all the three horses inoculated with CO06 seroconverted, they showed only mild clinical signs and two of them showed no virus shedding. CO06 had reduced binding to NeuGcα2‐3Gal.

Discussion  Our results demonstrated that CO06 had reduced proliferation ability and pathogenicity in horses. As the recognition of NeuGcα2‐3Gal by EIV is known to be essential for binding to the equine respiratory system, the decreased binding of CO06 to NeuGcα2‐3Gal may be one of the important factors that reduces the proliferation ability and pathogenicity of CO06 in horses.
Bayesian reconstitution of environmental change from disparate historical records: hedgerow loss and farmland bird declines
Authors: Cornulier Thomas , Robinson Robert A. , Elston David , Lambin Xavier , Sutherland William J. , Benton Tim G.
Published: July 2010

1. Understanding the mechanisms by which environmental change has impacted natural processes typically requires good time series for the environmental change. Unfortunately, other than for climate, detailed time series of historical environments are scarce. In many instances, researchers can only collate disparate and sometimes fragmented information from the literature or from historical or pre‐historical sources.

2. Here, we apply modern statistical methods to reconstruct a recent historical time series of environmental change from sparse data collected from heterogeneous sources. Specifically, we deal with record irregularity and the varying levels of uncertainty associated with each datum using state‐space models in a hierarchical Bayesian framework.

3. As an example, we reconstruct a time series of a simple landscape feature (hedgerow length) over a large spatial scale (Britain) over a long‐time period (50 years), by combining both stock estimates and rate of change estimates, gathered from different historical sources.

4. We illustrate the utility of the method by relating the population trends of a hedgerow‐nesting passerine bird, the yellowhammer Emberiza citrinella to the reconstructed trends in hedgerow length. Population density was closely related to hedgerow availability, suggesting a potential key role for nesting habitat loss in the yellowhammer decline.

5. The modelling framework we used is flexible and general. The method can be adapted to reconstruct time series of any environmental variables from a variety of sparse and heterogeneous historical sources.