bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyamine pathway contributes to the pathogenesis of Parkinson disease
Authors: Lewandowski Nicole M. , Ju Shulin , Verbitsky Miguel , Ross Barbara , Geddie Melissa L. , Rockenstein Edward , Adame Anthony , Muhammad Alim , Vonsattel Jean Paul , Ringe Dagmar , Cote Lucien , Lindquist Susan , Masliah Eliezer , Petsko Gregory A. , Marder Karen , Clark Lorraine N. , Small Scott A.
Published: September 2010

The full complement of molecular pathways contributing to the pathogenesis of Parkinson disease (PD) remains unknown. Here we address this issue by taking a broad approach, beginning by using functional MRI to identify brainstem regions differentially affected and resistant to the disease. Relying on these imaging findings, we then profiled gene expression levels from postmortem brainstem regions, identifying a disease-related decrease in the expression of the catabolic polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a range of studies were completed to support the pathogenicity of this finding. First, to test for a causal link between polyamines and α-synuclein toxicity, we investigated a yeast model expressing α-synuclein. Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology, we investigated a mouse model expressing α-synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, whereas Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, to test for a genetic link, we sequenced the SAT1 gene and a rare but unique disease-associated variant was identified. Taken together, the findings from human patients, yeast, and a mouse model implicate the polyamine pathway in PD pathogenesis.
Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production
Authors: Bozec Aline , Bakiri Latifa , Jimenez Maria , Schinke Thorsten , Amling Michael , Wagner Erwin F.
Published: September 2010

The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2–deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2–overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1α2 (col1α2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os’s) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans.
Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain–dependent manner
Authors: Kranich Jan , Krautler Nike Julia , Falsig Jeppe , Ballmer Boris , Li Shulei , Hutter Gregor , Schwarz Petra , Moos Rita , Julius Christian , Miele Gino , Aguzzi Adriano
Published: September 2010

Progressive accumulation of PrPSc, a hallmark of prion diseases, occurs when conversion of PrPC into PrPSc is faster than PrPSc clearance. Engulfment of apoptotic bodies by phagocytes is mediated by Mfge8 (milk fat globule epidermal growth factor 8). In this study, we show that brain Mfge8 is primarily produced by astrocytes. Mfge8 ablation induced accelerated prion disease and reduced clearance of cerebellar apoptotic bodies in vivo, as well as excessive PrPSc accumulation and increased prion titers in prion-infected C57BL/6 × 129Sv mice and organotypic cerebellar slices derived therefrom. These phenotypes correlated with the presence of 129Sv genomic markers in hybrid mice and were not observed in inbred C57BL/6 Mfge8−/− mice, suggesting the existence of additional strain-specific genetic modifiers. Because Mfge8 receptors are expressed by microglia and depletion of microglia increases PrPSc accumulation in organotypic cerebellar slices, we conclude that engulfment of apoptotic bodies by microglia may be an important pathway of prion clearance controlled by astrocyte-borne Mfge8.
Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation
Authors: Huggenberger Reto , Ullmann Stefan , Proulx Steven T. , Pytowski Bronislaw , Alitalo Kari , Detmar Michael
Published: September 2010

The role of lymphangiogenesis in inflammation has remained unclear. To investigate the role of lymphatic versus blood vasculature in chronic skin inflammation, we inhibited vascular endothelial growth factor (VEGF) receptor (VEGFR) signaling by function-blocking antibodies in the established keratin 14 (K14)–VEGF-A transgenic (Tg) mouse model of chronic cutaneous inflammation. Although treatment with an anti–VEGFR-2 antibody inhibited skin inflammation, epidermal hyperplasia, inflammatory infiltration, and angiogenesis, systemic inhibition of VEGFR-3, surprisingly, increased inflammatory edema formation and inflammatory cell accumulation despite inhibition of lymphangiogenesis. Importantly, chronic Tg delivery of the lymphangiogenic factor VEGF-C to the skin of K14-VEGF-A mice completely inhibited development of chronic skin inflammation, epidermal hyperplasia and abnormal differentiation, and accumulation of CD8 T cells. Similar results were found after Tg delivery of mouse VEGF-D that only activates VEGFR-3 but not VEGFR-2. Moreover, intracutaneous injection of recombinant VEGF-C156S, which only activates VEGFR-3, significantly reduced inflammation. Although lymphatic drainage was inhibited in chronic skin inflammation, it was enhanced by Tg VEGF-C delivery. Together, these results reveal an unanticipated active role of lymphatic vessels in controlling chronic inflammation. Stimulation of functional lymphangiogenesis via VEGFR-3, in addition to antiangiogenic therapy, might therefore serve as a novel strategy to treat chronic inflammatory disorders of the skin and possibly also other organs.
Type I interferon: friend or foe?
Authors: Trinchieri Giorgio
Published: September 2010

Although the role of type I interferon (IFN) in the protection against viral infections has been known and studied for decades, its role in other immunologically relevant scenarios, including bacterial infections, shock, autoimmunity, and cancer, is less well defined and potentially much more complicated.
A unified index of sequence quality and contig overlap for DNA barcoding
Authors: Little Damon P.
Published: September 2010

Summary: Barcode quality index (B) is a novel, unified measure of sequence quality and contig overlap tailored to the needs of DNA barcoding. Re-analysis of published data demonstrates the utility of B.

Availability and Implementation: A GPL PERL script is available for download (http://www.nybg.org/files/scientists/dlittle/B.html).

Contact:  dlittle@nybg.org
Acute pulmonary oedema: clinical characteristics, prognostic factors, and in‐hospital management
Authors: Parissis John T. , Nikolaou Maria , Mebazaa Alexandre , Ikonomidis Ignatios , Delgado Juan , Vilas‐Boas Fabio , Paraskevaidis Ioannis , Mc Lean Antony , Kremastinos Dimitrios , Follath Ferenc
Published: September 2010

Aims

Acute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7%) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM‐HF).

Methods and results

ALARM‐HF included a total of 4953 patients hospitalized for AHF in Europe, Latin America, and Australia. The final diagnosis was made at discharge, and patients were classified according to European Society of Cardiology guidelines. Patients with APE had higher in‐hospital mortality (7.4 vs. 6.0%, P = 0.057) compared with ADHF patients (n = 1911, 38.5%), and APE patients exhibited higher systolic blood pressures (P < 0.001) at admission and higher left ventricular ejection fraction (LVEF, P < 0.01) than those with ADHF. These patients also had a higher prevalence of diabetes (P < 0.01), arterial hypertension (P < 0.001), peripheral vascular disease (P < 0.001), and chronic renal disease (P < 0.05). They were also more likely to receive intravenous (i.v.) diuretics (P < 0.001), i.v. nitrates (P < 0.01), dopamine (P < 0.05), and non‐invasive ventilation (P < 0.001). Low systolic blood pressure (P < 0.001), low LVEF (<0.05), serum creatinine ≥1.4 mg/dL (P < 0.001), history of cardiomyopathy (P < 0.05), and previous cardiovascular event (P < 0.001) were independently associated with increased in‐hospital mortality in the APE population.

Conclusion

APE differs in clinical profile, in‐hospital management, and mortality compared with ADHF. Admission characteristics (systolic blood pressure and LVEF), renal function, and history may identify high‐risk APE patients.
VdSNF1, the Sucrose Nonfermenting Protein Kinase Gene ofVerticillium dahliae, Is Required for Virulence and Expression of Genes Involved in Cell-Wall Degradation
Authors: Tzima Aliki K. , Paplomatas Epaminondas J. , Rauyaree Payungsak , Ospina-Giraldo Manuel D. , Kang Seogchan
Published: September 2010

Verticillium dahliae is a soilborne fungus causing vascular wilt in a diverse array of plant species. Its virulence has been attributed, among other factors, to the activity of hydrolytic cell wall–degrading enzymes (CWDE). The sucrose nonfermenting 1 gene (VdSNF1), which regulates catabolic repression, was disrupted in V. dahliae tomato race 1. Expression of CWDE in the resulting mutants was not induced in inductive medium and in simulated xylem fluid medium. Growth of the mutants was significantly reduced when grown with pectin or galactose as a carbon source whereas, with glucose, sucrose, and xylose, they grew similarly to wild-type and ectopic transformants. The mutants were severely impaired in virulence on tomato and eggplant (final disease severity reduced by an average of 87%). Microscopic observation of the infection behavior of a green fluorescent protein (gfp)-labeled VdSNF1 mutant (70ΔSF-gfp1) showed that it was defective in initial colonization of roots. Cross sections of tomato stem at the cotyledonary level showed that 70ΔSF-gfp1 colonized xylem vessels considerably less than the wild-type strain. The wild-type strain heavily colonized xylem vessels and adjacent parenchyma cells. Quantification of fungal biomass in plant tissues further confirmed reduced colonization of roots, stems, and cotyledons by 70ΔSF-gfp1 relative to that by the wild-type strain.
In vitro Assessment of Sclerotinia homoeocarpa Resistance to Fungicides and Plant Growth Regulators
Authors: Ok Chang-Ho , Popko James T. , Campbell-Nelson Katie , Jung Geunhwa
Published: September 2010

Dollar spot (caused by Sclerotinia homoeocarpa) is the most economically important turfgrass disease in North America. This disease is primarily controlled by fungicide applications on golf courses; however, fungicide resistance has been confirmed in three of the four systemic fungicide classes commonly used to control dollar spot. The main objective of this study was to evaluate S. homoeocarpa sensitivity to multiple chemical classes and cross-resistance among active ingredients within the same class; in particular, the association between the fungistatic effect of demethylation inhibitors (DMIs) and plant growth regulators (PGRs). Fifty-eight isolates were selected arbitrarily from four locations in the United States and assayed for in vitro sensitivity to six DMI, two dicarboximide, one carboximide, and one benzimidazole fungicide as well as three type II PGRs. A series of concentrations for each active ingredient was used to determine the mean 50% effective concentration (EC50) values and correlation coefficients were calculated for all active ingredients. The EC50 values of all active ingredients from the DMI class were highly correlated (P < 0.0001) to each other as well as to the one dicarboximide (iprodione) and two PGRs (flurprimidol and paclobutrazol). Isolates resistant to thiophanatemethyl had significantly higher EC50 values than sensitive isolates for all active ingredients assayed except for boscalid. Findings showed that multiple and cross-resistance has developed in S. homoeocarpa and that the two PGRs have a fungistatic effect on this pathogen similar to that of DMI fungicides. The high correlation of in vitro sensitivities among PGRs and DMI fungicides further suggests that PGRs may contribute to the selection of DMI-resistant isolates or facilitate decreased sensitivity to DMI fungicides in the field.
Quantification of Propagules of the Laurel Wilt Fungus and Other Mycangial Fungi from the Redbay Ambrosia Beetle,Xyleborus glabratus
Authors: Harrington T. C. , Fraedrich S. W.
Published: September 2010

The laurel wilt pathogen, Raffaelea lauricola, is a fungal symbiont of the redbay ambrosia beetle, Xyleborus glabratus, which is native to Asia and was believed to have brought R. lauricola with it to the southeastern United States. Individual X. glabratus beetles from six populations in South Carolina and Georgia were individually macerated in glass tissue grinders and serially diluted to quantify the CFU of fungal symbionts. Six species of Raffaelea were isolated, with up to four species from an individual adult beetle. The Raffaelea spp. were apparently within the protected, paired, mandibular mycangia because they were as numerous in heads as in whole beetles, and surface-sterilized heads or whole bodies yielded as many or more CFU as did nonsterilized heads or whole beetles. R. lauricola was isolated from 40 of the 41 beetles sampled, and it was isolated in the highest numbers, up to 30,000 CFU/beetle. Depending on the population sampled, R. subalba or R. ellipticospora was the next most frequently isolated species. R. arxii, R. fusca, and R. subfusca were only occasionally isolated. The laurel wilt pathogen apparently grows in a yeast phase within the mycangia in competition with other Raffaelea spp.
Some Consequences of Using the Horsfall-Barratt Scale for Hypothesis Testing
Authors: Bock C. H. , Gottwald T. R. , Parker P. E. , Ferrandino F. , Welham S. , van den Bosch F. , Parnell S.
Published: September 2010

Comparing treatment effects by hypothesis testing is a common practice in plant pathology. Nearest percent estimates (NPEs) of disease severity were compared with Horsfall-Barratt (H-B) scale data to explore whether there was an effect of assessment method on hypothesis testing. A simulation model based on field-collected data using leaves with disease severity of 0 to 60% was used; the relationship between NPEs and actual severity was linear, a hyperbolic function described the relationship between the standard deviation of the rater mean NPE and actual disease, and a lognormal distribution was assumed to describe the frequency of NPEs of specific actual disease severities by raters. Results of the simulation showed standard deviations of mean NPEs were consistently similar to the original rater standard deviation from the field-collected data; however, the standard deviations of the H-B scale data deviated from that of the original rater standard deviation, particularly at 20 to 50% severity, over which H-B scale grade intervals are widest; thus, it is over this range that differences in hypothesis testing are most likely to occur. To explore this, two normally distributed, hypothetical severity populations were compared using a t test with NPEs and H-B midpoint data. NPE data had a higher probability to reject the null hypothesis (H0) when H0 was false but greater sample size increased the probability to reject H0 for both methods, with the H-B scale data requiring up to a 50% greater sample size to attain the same probability to reject the H0 as NPEs when H0 was false. The increase in sample size resolves the increased sample variance caused by inaccurate individual estimates due to H-B scale midpoint scaling. As expected, various population characteristics influenced the probability to reject H0, including the difference between the two severity distribution means, their variability, and the ability of the raters. Inaccurate raters showed a similar probability to reject H0 when H0 was false using either assessment method but average and accurate raters had a greater probability to reject H0 when H0 was false using NPEs compared with H-B scale data. Accurate raters had, on average, better resolving power for estimating disease compared with that offered by the H-B scale and, therefore, the resulting sample variability was more representative of the population when sample size was limiting. Thus, there are various circumstances under which H-B scale data has a greater risk of failing to reject H0 when H0 is false (a type II error) compared with NPEs.
Modeling the Competition Between Viruses in a Complex Plant–Pathogen System
Authors: Amaku Marcos , Burattini Marcelo Nascimento , Coutinho Francisco Antonio Bezerra , Massad Eduardo
Published: September 2010

In this article, we propose a mathematical model that describes the competition between two plant virus strains (MAV and PAV) for both the host plant (oat) and their aphid vectors. We found that although PAV is transmitted by two aphids and MAV by only one, this fact, by itself, does not explain the complete replacement of MAV by PAV in New York State during the period from 1961 through 1976; an interpretation that is in agreement with the theories of A. G. Power. Also, although MAV wins the competition within aphids, we assumed that, in 1961, PAV mutated into a new variant such that this new variant was able to overcome MAV within the plants during a latent period. As shown below, this is sufficient to explain the swap of strains; that is, the dominant MAV was replaced by PAV, also in agreement with Power's expectations.
A Quantitative Review of Fungicide Efficacy for Managing Downy Mildew in Cucurbits
Authors: Ojiambo P. S. , Paul P. A. , Holmes G. J.
Published: September 2010

A meta-analysis of the effect of fungicides on cucurbit downy mildew was conducted using data previously published in Fungicide & Nematicide Tests and Plant Disease Management Reports from 2000 to 2008. Standardized mean effect size (the difference in disease intensity expressed in standard deviation units between the fungicide treatment and its corresponding untreated control) was calculated for each of the 105 field studies evaluating the effects of fungicides on cucurbit downy mildew. Fixed- and random-effects meta-analyses were performed on the log-transformed standardized mean effect sizes to estimate the overall mean effect size ([Formula: see text]), and to determine the variability in the effect size among studies. Fungicides led to a significant (P < 0.001) reduction in disease with an [Formula: see text] value of 1.198, indicating that, overall, fungicides were highly effective against cucurbit downy mildew. Fixed- and random-effects meta-analyses were then conducted to determine the effects of moderator variables on [Formula: see text]. The fixed-effects model resulted in narrower 95% confidence intervals and generally lower estimates of moderator subgroup mean effect size ([Formula: see text]) than the random-effects models. Fungicide efficacy was significantly (P < 0.001) greater in cucumber, with [Formula: see text] being 26.5% higher in cucumber than in other cucurbits. Year of study, number of sprays, and disease pressure in the control significantly (P < 0.001) affected [Formula: see text]. Fungicide efficacy was significantly lower during the 2004–05 season than prior to or after the 2004–05 season. Studies in which disease pressure was moderate had a significantly higher [Formula: see text] than studies with either low or high disease pressure. Fungicide efficacy was ≥22% in studies that received 5 to 6 sprays than in studies that received 1 to 4 or >6 sprays. Fungicide products led to a significant (P < 0.001) reduction in disease, although there was substantial between-study variability. The pyridinylmethyl-benzamide group of fungicides (fluopicolide) was the most effective, followed by the carbamate (propamocarb) and quinone inside inhibitors (cyazofamid) group of fungicides, while the carboxylic acid amide group (mandipropamid and dimethomorph) was the least effective. A combination of protectant and systemic fungicides resulted in a proportional increase in [Formula: see text] compared with sole application of either protectant or systemic fungicides.
Expression of p57kip2 in mouse and human testes
Authors: Kim Sung Tae , Gye Myung Chan
Published: September 2010

The expression of cyclin‐dependent kinases inhibitors, p57kip2, was investigated during the postnatal development of mouse testis, and in adult human testis. Expression of p57kip2 mRNA was higher in immature than pubertal or adult mouse testes. In postnatal day 7 (PND7) testes, moderate p57kip2 immunoreactivity was found in spermatogonia, but signal was heterogeneous among the spermatogonia. In PND14 testes onward, strong immunoreactivity of p57kip2 was found in the nuclei of early spermatocytes but not in the late pachytene stage onward. In PND28 and PND50 testes, p57kip2 immunoreactivity was varying among the seminiferous tubules. There was no visible signal in late pachytene stage onward. In Leydig cells, heterogeneous immunoreactivity of p57kip2 was found in immature testis and the signal intensity was higher in adult testis than immature ones. In Sertoli cells, weak or negligible immunoreactivity of p57kip2 was found. In human seminiferous tubule, strong immunoreactivity of p57kip2 was found in the nucleus of early spermatocytes, but not in the late pachytene spermatocytes onward and Sertoli cells. These results suggest the possible role of p57kip2 in the regulation of early spermatogonial proliferation, meiotic progression of early spermatocytes and differentiation of Leydig cells in testis.
PSYCHOLOGICAL, NEUROPSYCHOLOGICAL AND PHYSIOLOGICAL CORRELATES OF SERIOUS ANTISOCIAL BEHAVIOR IN ADOLESCENCE: THE ROLE OF SELF‐CONTROL*
Authors: CAUFFMAN ELIZABETH , STEINBERG LAURENCE , PIQUERO ALEX R.
Published: September 2010

Gottfredson and Hirschi claim that self‐control is the only enduring personal characteristic implicated in criminal activity. Other scholars, such as Moffitt and Rowe, claim that although self‐control is important, so are neuropsychological and physiological factors. This study attempts to adjudicate between these two positions by examining the ways in which neuropsychological factors, especially those relevant to executive function, biological factors, especially those relevant to autonomic reactivity, and self‐control interrelate to distinguish between offenders and nonoffenders. Data were obtained from adolescents attending public high schools in northern California and adolescents incarcerated in the California Youth Authority. Serious juvenile offenders evince lower resting heart rate, show poorer performance on tasks that activate cognitive functions mediated by the prefrontal cortex, especially those measuring spatial working memory, and score lower on measures of self‐control. Regression analyses indicated that although variations in self‐control distinguish between the two groups, so too do neuropsychological and biological factors, a result that both supports and refutes Gottfredson and Hirschi's contention. In contrast, variation in minor delinquency among high school students is unrelated to frontal lobe functioning and heart rate, but related to variations in self‐control.
Interactions between riparian shading and food supply: a seasonal comparison of effects on time budgets, space use and growth in Atlantic salmon Salmo salar
Authors: Orpwood J. E. , Armstrong J. D. , Griffiths S. W.
Published: September 2010

This study examines seasonal (winter v. summer) differences in space‐time budgets, food intake and growth of Atlantic salmon Salmo salar parr in a controlled, large‐scale stream environment, to examine the direction and magnitude of shifts in behaviour patterns as influenced by the availability of overhead cover and food supply. Salmo salar parr tested in the presence of overhead cover were significantly more nocturnal and occupied more peripheral positions than those tested in the absence of overhead cover. This increase in nocturnal activity was driven primarily by increased activity at night, accompanied by a reduction in daytime activity during winter. The presence of overhead cover had no effect on rates of food intake or growth for a given food supply in a given season. Growth rates were significantly higher for fish subjected to a high food supply than those subjected to a low food supply. Food supply did not affect the extent to which S. salar parr were nocturnal. These results were consistent between winter and summer. The use of riparian shading as a management technique to mitigate the effects of warming allows the adoption of more risk‐averse foraging behaviour and may be particularly beneficial in circumstances where it serves also to increase the availability of food.
A FIELD GUIDE TO THE RECORDING OF PARASITIC INFESTATION OF GAME ANIMALS
Authors: Sachs R. , Debbie J. G.
Published: September 2010

The importance of a survey of parasites in various game areas in East Africa is outlined both from the point of view of understanding the ecosystem and of exploiting its productivity. The commonly‐encountered parasites are described and their normal locations in the host are given. Standard ways of classifying and assessing the degree of infestation by these major parasites are suggested, and the most appropriate manner of preserving specimens for subsequent examination is noted. A check‐sheet for the recording of parasites in a post‐mortem examination of game animals is included. Such a check‐sheet, completed as suggested, together with adequate well‐labelled collections, should be of great value in building up a general picture of the incidence and degree of parasitic infestation of various host animals in East African game areas.
THE PRACTICAL ASPECTS OF IMPLEMENTING A CONTROLLED BURNING SCHEME IN THE KIDEPO VALLEY NATIONAL PARK (SECOND YEAR OF OPERATION)
Authors: Ross I. C. , Harrington G. N.
Published: September 2010

A controlled burning scheme, in conjunction with experimental plots, was necessary in order to investigate the effects of fire on tree regeneration in an area which otherwise suffers frequent uncontrolled fires and where an important tree species, Acacia gerrardii Benth.var. gerrardii, was failing to regenerate.

The second year's results are described. The scheme was not successful in excluding uncontrolled fires. However, further experience, indicating yet more problems, was gained.
BLACK RHINOCEROS IMMOBILIZATION UTILIZING A NEW TRANQUILLIZING AGENT
Authors: Denney Richard N.
Published: September 2010

Eleven black rhinoceroses were successfully immobilized, ten of them in the Arusha Chini area of Tanzania and one, a penned animal, near Nairobi. Of the total number, two were immobilized with Etorphine hydrochloride (M. 99) and acetylpromazine; six with a combination of Etorphine, acetylpromazine and a new tranquillizer, Azaperone; and three with Etorphine and Azaperone. In addition, one attempt at immobilization with a relatively new analgesic, Fentanyl, was not satisfactory at the dosage used, the animal being immobilized later with Etorphine and included in the eleven rhino described. Injection was accomplished on the ten Tanzania animals with Cap‐Chur equipment from a helicopter, and on the penned animal with a hand syringe. Specimens and data were collected from the immobilized rhino. They were then loaded into crates, given an antidote (nalorphine hydrobromide) intramuscularly, and then trucked to points of release or to holding pens. Immobilization data, weights, sexes, relative ages, rectal temperatures, respiratory rates and pulse rates are tabulated.
Influence of different degrees of liver impairment on the pharmacokinetics of clazosentan
Authors: Bruderer Shirin , Detishin Victor , Tsvitbaum Nahum , Dingemanse Jasper
Published: September 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Clazosentan is a selective endothelin A receptor antagonist, formulated for parenteral use, which is in clinical development for the treatment of aneurysmal subarachnoid haemorrhage.

• The human ADME study showed that most of clazosentan is excreted via the biliary route.

• The pharmacokinetics (PK) of clazosentan are similar in healthy subjects and those with severe renal impairment.

WHAT THIS STUDY ADDS

• The results of the present study showed that there was an increase in the exposure to clazosentan with increasing severity of liver impairment. Changes in PK in subjects with mild liver impairment compared with healthy subjects are unlikely to be clinically relevant.

• There are significant differences in the PK parameters of clazosentan in subjects with moderate and severe liver impairment compared with healthy subjects.

• The results of this study will allow confident dosing of clazosentan in individuals with moderate and severe liver impairment.

AIM To investigate the effect of mild, moderate and severe liver impairment on the pharmacokinetics (PK), tolerability and safety of clazosentan, an intravenous endothelin receptor antagonist.

METHODS Healthy subjects with normal liver function (n= 8), subjects with mild (Child Pugh A, n= 8), and with moderate (Child‐Pugh B, n= 8) liver impairment received a continuous intravenous infusion of 1 mg h−1 and subjects with severe liver impairment (Child Pugh C, n= 8) received a continuous intravenous infusion of 0.5 mg h−1 clazosentan for a duration of 6 h. The pharmacokinetic (PK) parameters of clazosentan were determined by both model‐independent and model‐dependent methods.

RESULTS Mean plasma concentrations of clazosentan increased with increasing severity of liver impairment. Geometric means of area under the plasma concentration–time curve from 0 to infinity (AUC(0,∞)) were 1.41‐ (90% CI 1.04, 1.90), 2.37‐ (90% CI 1.75, 3.19), and 3.79‐ (90% CI 2.81, 5.11) fold higher in subjects with mild, moderate and severe liver impairment, respectively, compared with healthy subjects. Similar results were obtained by non‐compartmental and two‐compartmental analysis. A significant positive correlation between clazosentan AUC(0,∞) and Child‐Pugh score (r= 0.83), bilirubin (r= 0.78) and prothrombin time (r= 0.62), and a significant negative correlation with albumin concentrationl (r= 0.71) was observed. Administration of clazosentan was well tolerated in all groups.

CONCLUSIONS The increase in exposure to clazosentan in Child‐Pugh A patients is not expected to be clinically relevant and no dose adjustment for these patients is proposed. It is recommended to reduce the dose of clazosentan to half in Child‐Pugh B and to one fourth in Child‐Pugh C patients.
High‐affinity immunoglobulin E receptor expression is increased in large and small airways in fatal asthma
Authors: Den Otter I. , Silva L. F. F. , Carvalho A. L. N. , Pires‐Neto R. C. , Annoni R. , Ferreira D. S. , Bajema I. , Van Schadewijk A. , Rabe K. F. , Dolhnikoff M. , Sterk P. J. , Hiemstra P. S. , Mauad T.
Published: September 2010

Background
IgE and its high‐affinity receptor FcɛRI play an important role in allergy and asthma. The distribution of FcɛRI expression in the airways and within the airway wall, however, is largely unknown.

Objective
In this study, we aimed to map the distribution of FcɛRI in different layers of large airways (LA) and small airways (SA) in lung tissue from non‐smoking and smoking patients who died of asthma [fatal asthma (FA)] and non‐smoking controls (CTR).

Methods
Postmortem lung tissue from 24 cases of non‐smoking FA, 13 smoking FA patients and from 19 subjects who died of non‐pulmonary causes (CTR) was immunohistochemically stained for FcɛRI and AA1 (mast cell tryptase marker). The expression of these markers was analysed in inner, muscle, and outer layers of both LA and SA by image analysis.

Results
FcɛRI expression was higher in non‐smoking and smoking FA compared with CTR in the inner and outer layer of SA. In the outer layer of LA, FcɛRI expression was higher in non‐smoking FA compared with CTR. AA1 was higher in non‐smoking FA compared with smoking FA and CTR in the outer layer of the SA, which was correlated with FcɛRI in this layer.

Conclusion
Our results show that the expression of FcɛRI is higher in both LA and SA in FA compared with CTR. These differences are predominantly found in the outer layer where they can be attributed in part to the increased mast cell numbers. These results indicate an increased capacity to mount IgE‐mediated reactions in FA, both in LA and SA.

Cite this as: I. den Otter, L. F. F. Silva, A. L. N. Carvalho, R. C. Pires‐Neto, R. Annoni, D. S. Ferreira, I. Bajema, A. van Schadewijk, K. F. Rabe, M. Dolhnikoff, P. J. Sterk, P. S. Hiemstra and T. Mauad, Clinical & Experimental Allergy, 2010 (40) 1473–1481.
Allergy to rodents: an update
Authors: Jeal H. , Jones M.
Published: September 2010

Allergy to rodents in the workplace is an important occupational health problem affecting research, pharmaceutical and toxicological sectors and can have a serious impact on employees working in this area. Despite measures to reduce aeroallergen exposures to rodents in the workplace, there are few signs that this occupational health problem is declining. Rodent allergens are well characterized and exposure–response relationships have been demonstrated to be complex. More recently, the importance of rodent allergens outside of the workplace has been demonstrated in several studies of individuals with asthma. This review focuses on rodent allergy both in the workplace and in the home and examines the complex exposure–response relationships between allergen exposure and sensitization and asthma. Risk factors for rodent allergy and mechanisms of tolerance to rodent allergens are discussed.

Cite this as: H. Jeal and M. Jones, Clinical & Experimental Allergy, 2010 (40) 1593–1601.
Caesarean sections and risk of wheezing in childhood and adolescence: data from two birth cohort studies in Brazil
Authors: Menezes A. M. B. , Hallal P. C. , Matijasevich A. M. , Barros A. J. D. , Horta B. L. , Araujo C. L. P. , Gigante D. P. , Santos I. S. , Minten G. , Domingues M. R. , Dumith S. C. , Barros F. C.
Published: September 2010

Cite this as: A. M. B. Menezes,P. C. Hallal, A. M. Matijasevich,A. J. D. Barros, B. L. Horta, C. L. P. Araujo,D. P. Gigante, I. S. Santos, G. Minten,M. R. Domingues, S. C. Dumith and F. C. Barros, Clinical & Experimental Allergy, 2011 (41) 218–223.

Background
There is evidence from two meta‐analyses that children born through caesarean section (C‐section) may have an increased risk of developing asthma compared with those born through vaginal delivery.

Objective
To evaluate the association between mode of delivery and wheezing (current and persistent) in childhood and adolescence, in two birth cohort studies in Brazil.

Methods
The outcome variable was based on the International Study of Allergy and Asthma questionnaire, which collects information about wheezing within the 12 months before the interview. Persistent wheezing was defined when it was present in more than one follow‐up at different ages, in the 1993 cohort. The questions were asked to mothers when children were aged 4 years (1993 and 2004 cohorts) and directly to cohort participants at 11 and 15 years (1993 cohort). Mode of delivery was collected by the research team of each cohort when children were born.

Results
Response rates in the last follow‐up visit of the 1993 and 2004 cohorts were 85% and 92%, respectively. The prevalence of current wheezing increased from 20% to 28% at 4 years from 1993 to 2004; at 11 and 15 years, the prevalence was around 14% and 12%, in the 1993 cohort. The proportion of C‐sections increased from 30.5% to 45% between 1993 and 2004. In each cohort, the prevalence of current wheezing was similar among children born through vaginal and C‐section. The risk for persistent wheezing in the 1993 cohort was higher among girls born through C‐section than boys.

Conclusion
Despite the increase in the proportion of C‐section in two cohorts in Southern Brazil, we found no evidence of an association between mode of delivery and the subsequent risk of wheezing. Among girls, although there was no statistical significance, the risk was higher for those born by C‐section, especially regarding persistent wheezing.
Rapid migration of thymic emigrants to the colonic mucosa in ulcerative colitis patients
Authors: Elgbratt K , Kurlberg G , Hahn-Zohric M , Hörnquist E Hultgren
Published: September 2010

Inflammatory bowel disease (IBD) is associated with imbalances of the local intestinal immune responses, with dysregulated CD4+ T cells contributing to the chronic inflammation. Having demonstrated altered T cell maturation in the thymus in two different mouse models of colitis, we set out to investigate whether abnormalities in T cell maturation is present in patients with ulcerative colitis (UC) or Crohn's disease (CD). Specimens were obtained from peripheral blood (CD; n = 14, UC; n = 22), colon and small intestinal specimens (CD; n = 6, UC; n = 13). As controls, peripheral blood specimens were obtained from healthy volunteers, patients with adenocarcinomas (n = 18) and colonic specimens from patients with adenocarcinomas (n = 14). Recent thymic emigrants were estimated by analysis of the normalized ratio of T cell receptor excision circles (TRECs) by real-time polymerase chain reaction (PCR). The frequency of naive- and proliferating T lymphocytes and markers of extrathymic T cell maturation in the mucosa was analyzed by flow cytometry and real time-PCR. TREC levels in peripheral blood T lymphocytes were similar between IBD patients and controls. In contrast, UC patients demonstrated significantly increased levels of TRECs both in intraepithelial and lamina propria lymphocytes from the colonic mucosa compared to patients with adenocarcinomas and CD. However, markers for extrathymic T cell maturation in the mucosa were not different between controls and IBD patients. The increased TREC levels in mucosal but not peripheral blood lymphocytes in UC patients in the absence of increased extrathymic maturation in situ in the mucosa together demonstrate that recent thymic emigrants are recruited rapidly to the inflamed mucosa of these patients.
Increased morbidity and mortality in murine cytomegalovirus-infected mice following allogeneic bone marrow transplant is associated with reduced surface decay accelerating factor expression
Authors: El-Amouri I S , Bani-Ahmad M , Tang-Feldman Y , Lin F , Ko C , Pomeroy C , Oakley O R
Published: September 2010

Infection with cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following allogeneic bone marrow transplantation (allo-BMT). The manifestations of CMV infection can range from neurological and haematological abnormalities to diminished graft survival and, in extreme cases, death. Many clinical studies have shown a direct correlation between cytomegalovirus infection and increased morbidity and mortality post allo-BMT, yet the exact mechanism is not well understood. Although driven primarily by T cell responses, the role of complement activation in acute and chronic graft-versus-host disease (GVHD) has also become more evident in recent years. The present studies were performed to examine the effects of murine cytomegalovirus (MCMV) infection on decay accelerating factor (DAF) and MCMVs role in exacerbating morbidity and mortality post-allo-BMT. Mice infected previously with a sublethal dose of MCMV (1 × 105 plaque-forming units) have reduced expression of DAF on lung tissues and lymphocytes following allo-BMT. More importantly, mortality rates post-allo-BMT in recipient DAF knock-out mice receiving wild-type bone marrow are increased, similar to wild-type MCMV-infected recipient mice. Similarly, DAF knock-out mice showed greater intracellular interferon (IFN)-γ production by lung CD8 T cells, and infection with MCMV further exacerbated both intracellular IFN-γ production by CD8 T cells and mortality rates post-allo-BMT. Together, these data support the hypothesis that MCMV infection augments morbidity and mortality post-allo-BMT by reducing surface DAF expression.
Fine Needle Aspiration Cytodiagnosis of A Carcinoid Tumour of the Male Breast
Authors: GUPTA R. K. , SIMPSON J. S.
Published: September 2010

The diagnosis of a primary carcinoid tumour of the breast in a 38‐year‐old male was initially made from a fine needle aspiration sample. the cytodiagnosis was supported by the histochemical demonstration of Grimelius‐positive granules in tumour cells which were also found in tissue removed in a subsequent biopsy. an immunocytochemical study using markers for neuron‐specific enolase and chromagranin in the aspirated sample and tissue was found to be negative. A total mastectomy with axillary node dissection was performed which showed no residual or metastatic tumour. No primary tumour was found elsewhere.
Seasonal patterns of parasitism and differential susceptibility among species in macrolepidopteran assemblages on Salix nigra (Marsh) and Acer negundo L.
Authors: BARBOSA PEDRO , CALDAS ASTRID
Published: September 2010

Abstract 1. Previous research has demonstrated that parasitism of larval macrolepidoptera on Acer negundo (box elder) is greater than that of larvae on Salix nigra.

2. In this study, percentage larval parasitism of species on box elder and black willow was calculated for distinct portions of the season, to determine if the higher levels of parasitism on box elder resulted from greater parasitism during a particular portion of the season.

3. Larval parasitism was higher on box elder regardless of the portion of the season; however, the seasonal pattern of parasitism differed for each tree species, i.e. late‐season box elder parasitism increased and late‐season black willow parasitism decreased relative to early‐ and mid‐season parasitism.

4. The degree to which higher levels of parasitism were associated with host and parasitoid traits such as average larval abundance, number of species, type of host, and parasitoid species load of macrolepidoptera, as well as average number of species of parasitoids during each portion of the season was determined.

5. In addition, the possibility that differences in the pattern of parasitism on box elder and black willow were caused by the presence of a greater number of numerically dominant parasitoid species in late‐season box elder was investigated.

6. None of the variables, other than type of host species, were associated with higher levels of parasitism in late‐season box elder.

7. Late‐season, single‐tree species on box elder (i.e. species that occurred only on box elder) were more heavily parasitised, compared with dual‐tree species. This difference was not observed earlier in the season nor on black willow.

8. Further, single‐tree species on late‐season box elder included three numerically dominant species that suffered significantly greater larval parasitism than any other type of species on either of the two trees.

9. This study supported previous predictions, that suggested the importance of larval coloration: there was a higher proportion of green larvae among the most highly parasitised host species, i.e. single‐tree, numerically dominant species.
Life‐history, genotypic, and environmental correlates of clutch size in the Glanville fritillary butterfly
Authors: SAASTAMOINEN MARJO
Published: September 2010

Abstract1. Glanville fritillary butterfly (Melitaea cinxia) females lay up to 10 clutches of 50–300 eggs in their lifetime. Clutch size is an important life‐history trait as larval group size affects survival throughout larval development.

2. Two experiments were carried out in a large population cage in the field to investigate the life‐history and environmental correlates of clutch size.

3. Clutch size decreased with the cumulative number of eggs laid previously, increased with both female body weight and the number of days between consecutive clutches.

4. Genotypic differences among females in the glycolytic enzyme phosphoglucose isomerase had a significant influence on clutch size, partly because females of particular genotypes were able to initiate oviposition earlier in the day and thereby take advantage of the most favourable environmental conditions for oviposition.

5. Factors influencing clutch size were partly different in two summers, indicating the modulating effect of prevailing environmental conditions on reproductive performance.
Seasonal phenotypic plasticity of wing melanisation in the cabbage white butterfly, Pieris rapae L. (Lepidoptera: Pieridae)
Authors: STOEHR ANDREW M. , GOUX HIPPOLYTE
Published: September 2010

Abstract 1. Effective thermoregulation is crucial for the fitness of small flying insects. Phenotypic plasticity of the ventral hindwing of pierid butterflies is widely recognised as adaptive for effective thermoregulation. Butterflies eclosing in cooler environments have more heavily melanised wings that absorb solar radiation, thus allowing flight under these cool conditions.

2. Many pierids also exhibit phenotypic plasticity of dorsal forewing melanisation but in this case, cooler environments reduce melanisation. It has been hypothesised that this plasticity is also adaptive because it increases solar reflection from the wing surfaces onto the body in certain basking postures.

3. The degree of seasonal variation in ventral hindwing and dorsal forewing melanisation of wild‐caught Pieris rapae was quantified to determine if it shows patterns of plasticity similar to that documented for other Pieris species.

4. Male wing melanisation on both wing surfaces shows the characteristic seasonal, adaptive plasticity. However, only some dorsal forewing pattern elements of females conformed to the predictions of the hypothesis of adaptive dorsal forewing melanisation. Sexual dimorphism of wing pattern plasticity may result from, and/or affect, sexual dimorphism of behaviour and physiology of these butterflies.