bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulating neuroregeneration as a therapeutic drug approach for traumatic brain injury
Authors: Mueller Bernhard K , Mueller Reinhold , Schoemaker Hans
Published: May 2009

Traumatic brain injury, a silent epidemic of modern societies, is a largely neglected area in drug development and no drug is currently available for the treatment of patients suffering from brain trauma. Despite this grim situation, much progress has been made over the last two decades in closely related medical indications, such as spinal cord injury, giving rise to a more optimistic approach to drug development in brain trauma. Fundamental insights have been gained with animal models of central nervous system (CNS) trauma and spinal cord injury. Neuroregenerative drug candidates have been identified and two of these have progressed to clinical development for spinal cord injury patients. If successful, these drug candidates may be used to treat brain trauma patients. Significant progress has also been made in understanding the fundamental molecular mechanism underlying irreversible axonal growth arrest in the injured CNS of higher mammals. From these studies, we have learned that the axonal retraction bulb, previously regarded as a marker for failure of regenerative growth, is not static but dynamic and, therefore, amenable to pharmacotherapeutic approaches. With the development of modified magnetic resonance imaging methods, fibre tracts can be visualised in the living human brain and such imaging methods will soon be used to evaluate the neuroregenerative potential of drug candidates. These significant advances are expected to fundamentally change the often hopeless situation of brain trauma patients and will be the first step towards overcoming the silent epidemic of brain injury.
Mast cell degranulation – a mechanism for the anti‐arrhythmic effect of endothelin‐1?
Authors: Walsh SK , Kane KA , Wainwright CL
Published: May 2009

Background and purpose: The aim of this study was to investigate whether the previously reported anti‐arrhythmic effect of endothelin‐1 (ET‐1) is mediated by degranulation of cardiac mast cells prior to myocardial ischaemia.

Experimental approach: Male Sprague‐Dawley rats received either ET‐1 (1.6 nmol·kg−1) in the presence or absence of disodium cromoglycate (DSCG; 20 mg·kg−1·h−1) prior to coronary artery occlusion (CAO). In separate experiments rats were given compound 48/80 (50 µg·kg−1) to compare the effects of ET‐1 with those of a known mast cell degranulator. Ischaemia‐induced ventricular arrhythmias were detected through continuous monitoring of a lead I electrocardiogram. After 30 min of CAO, the hearts were removed and mast cell degranulation determined by histological analysis. A parallel series of sham groups were performed to determine the direct effects of ET‐1 and compound 48/80 on mast cell degranulation in the absence of ischaemia.

Key results: ET‐1 and compound 48/80 both exerted profound anti‐arrhythmic effects, significantly reducing the total number of ventricular ectopic beats (P< 0.001) and the incidence of ventricular fibrillation (P< 0.05). These anti‐arrhythmic effects were abolished by concomitant DSCG infusion prior to CAO. In sham animals ET‐1 and compound 48/80 both induced mast cell degranulation (P< 0.001), an effect which was abolished by DSCG, confirming their ability to induce degranulation of mast cells.

Conclusions and implications: These results demonstrate for the first time that when given prior to ischaemia ET‐1 mediates its anti‐arrhythmic effects, at least in part, via cardiac mast cell degranulation.
P633H, a novel dual agonist at peroxisome proliferator‐activated receptors α and γ, with different anti‐diabetic effects in db/db and KK‐Ay mice
Authors: Chen Wei , Zhou Xin‐Bo , Liu Hong‐Ying , Xu Cheng , Wang Li‐Li , Li Song
Published: May 2009

Background and purpose:  Peroxisome proliferator‐activated receptors (PPARs) are attractive targets for the treatment of type 2 diabetes and the metabolic syndrome. P633H (2‐[4‐(2‐Fluoro‐benzenesulphonyl)‐piperazin‐1‐yl]‐3‐{4‐[2‐(5‐methyl‐2‐phenyl‐oxazol‐4‐yl)‐ethoxy]‐phenyl}‐propionic acid), a novel PPARα/γ dual agonist, was investigated for its very different effects on insulin resistance and dyslipidemia in db/db and KK‐Ay mice.

Experimental approach:  The action of P633H at PPARα/γ was characterized by using transactivation assays. Functional activation of PPARα/γin vitro was confirmed by pre‐adipocyte differentiation and regulation of target gene expression. Anti‐diabetic studies were performed in two different diabetic mice models in vivo.

Key results:  P633H activated both PPARα and PPAR γ, (with EC50 values of 0.012 µmol and 0.032 µmol respectively). Additionally, P633H promoted pre‐adipocyte differentiation, up‐regulated expression of adipose specific transport protein (aP2) mRNA (3T3‐Ll cells) and acyl‐CoA oxidase mRNA (LO2 cells). In db/db mice, P633H reduced serum glucose, insulin, triglycerides, non‐esterified fatty acids and liver triglycerides. It also improved glucose intolerance without affecting food intake and body weight after 15 days of treatment. However in KK‐Ay mice, hyperglycaemia, dyslipidemia and impaired glucose tolerance were not relieved even after a 25 day treatment with P633H. Further studies with real‐time PCR and electron microscopy revealed that P633H promoted progression of diabetes in KK‐Ay mice by increasing hepatic gluconeogenesis and exacerbating pancreatic pathology.

Conclusion and implications:  Although P633H was a high‐potency PPARα/γ dual agonist, with good functional activity in vitro, it produced opposing anti‐diabetic effects in db/db and KK‐Ay mice.
Selective PARP‐2 inhibitors increase apoptosis in hippocampal slices but protect cortical cells in models of post‐ischaemic brain damage
Authors: Moroni F , Formentini L , Gerace E , Camaioni E , Pellegrini‐Giampietro D E , Chiarugi A , Pellicciari R
Published: May 2009

Background and purpose:  Poly(ADP‐ribose) polymerases (PARP)‐1 and PARP‐2 play complementary tasks in the maintenance of genomic integrity, but their role in cell death or survival processes is rather different. A recently described series of selective PARP‐2 inhibitors (UPF‐1035, UPF‐1069) were used to study the role of PARP‐1 and PARP‐2 in post‐ischaemic brain damage.

Experimental approach:  We evaluated post‐ischaemic brain damage in two different in vitro models: rat organotypic hippocampal slices exposed to oxygen‐glucose deprivation (OGD) for 20–30 min, a model characterized by apoptosis‐like cell death and mouse mixed cortical cell cultures exposed to 60 min OGD, a model in which cells die with mostly necrosis‐like features.

Key results:  In organotypic hippocampal slices, PARP‐2 inhibition with UPF‐1069 (0.01–1 µmol·L−1) caused a concentration‐dependent exacerbation (up to 155%) of OGD‐induced CA1 pyramidal cell death. Higher concentrations, acting on both PARP‐1 and PARP‐2, had no effect on OGD injury. In mouse mixed cortical cells exposed to OGD, on the contrary, UPF‐1069 (1–10 µmol·L−1) significantly reduced post‐ischaemic damage.

Conclusion and implications:  Selective PARP‐2 inhibitors increased post‐OGD cell death in a model characterized by loss of neurons through a caspase‐dependent, apoptosis‐like process (hippocampal slice cultures), but they reduced post‐OGD damage and increased cell survival in a model characterized by a necrosis‐like process (cortical neurons). UPF‐1069 may be a valuable tool to explore the function of PARP‐2 in biological systems and to examine the different roles of PARP isoenzymes in the mechanisms of cell death and survival.
The Empire's War Recalled: Recent Writing on the Western Front Experience of Britain, Ireland, Australia, Canada, India, New Zealand, South Africa and the West Indies
Authors: Connor John
Published: May 2009

The ninetieth anniversary of the end of the First World War in 2008 was marked with the publication of a number of works in many parts of what was once the British Empire. We saw an increased output in publications on the Western Front. In Britain, the recent literature attempts to rehabilitate Douglas Haig and define the ‘learning curve’ that enabled the British army to defeat Germany in 1918. In Australia, Canada and New Zealand, the performance of their soldiers on the Western Front is seen as central to national identity and this now focuses on military success rather than sacrifice in a futile war. In India, South Africa and Jamaica, there is a renewed interest in linking the First World War to national identities based on the independence or liberation struggle. In Ireland, the Great War is seen as a shared experience that can link the Nationalist and Unionist traditions in Northern Ireland and the Republic. The article concludes that this interest in the Western Front will continue into the next decade in the lead‐up to the centenary of the First World War.
Rural Woman and Modernity in Globalizing China: Seeing Jia Zhangke's The World
Authors: GAETANO ARIANNE
Published: May 2009

In this article, I consider Jia Zhangke's 2004 film The World (shijie) as a tool for critical thinking about the challenges of modernity and globalization for internal migrants in contemporary China, especially young rural women working in Beijing, and the gender politics of their representation. A close reading of the film, juxtaposed with ethnographic studies on China's internal migration and rural women, demonstrates that The World's visual and narrative techniques provide valuable insight into the disjuncture between transnational imaginaries and local material conditions, which together contour migrants' experience of globalization. However, to effectively deliver its critique, The World relies upon a chauvinistic convention of using “rural woman” as a sign of social ills, rather than an agent of social change. I suggest that deconstructing the gendering of modernity and national identity by recognizing rural migrant women as agents of globalization can mitigate the dire message of  The World that, ultimately, rural woman and modernity are incompatible, as are, allegorically, China and globalization.
The Marigold Trail: A Study of Robert Gardner's Forest of Bliss (1985)
Authors: SINHA SURYANANDINI
Published: May 2009

Robert Gardner's landmark film Forest of Bliss (1985) spawned much criticism and debate in the domain of visual anthropology, articulated through a spate of writing during the years 1988–89 in the Society for Visual Anthropology Newsletter. Two decades later, multiple possibilities of interpreting this film enliven it with the same questions and more, even as the timeless city of Banaras remains consistent in its visual vocabulary in an India of the 21st century. This essay explores the symbolic nature of materiality that imbues everyday living in the holy city, articulated in Gardner's ethnographic understanding through the visual narrative that it weaves. Several recurrent motifs, such as the marigold flower, saturate this visual document with points of entry that open pathways of reading and interpretation, confirming Gardner's pioneering initiative within methodology and technique in visual anthropology.
Photographic Evidence for Southern Plains Armor
Authors: GELO DANIEL J. , JONES III LAWRENCE T.
Published: May 2009

The use of armor by Plains Indians is one of the more obscure culture traits of the area. Although there are enough occasional references in early historical works to ascertain armor use and reconstruct some of the particulars, pictorial and artifact evidence has been virtually nonexistent. The recent discovery by Lawrence T. Jones III of a photographic carte de visite portraying an unknown Comanche, Kiowa, or Kiowa Apache (Plains Apache) man circa 1871 provides intriguing evidence for armor on the Southern Plains. This find also prompts discussion of related cultural practices and the ethnohistorical potential of photograph analysis.
Health‐beneficial effects of probiotics: Its mode of action
Authors: OHASHI Yuji , USHIDA Kazunari
Published: May 2009

It is now widely recognized that probiotics have health‐beneficial effects on humans and animals. Probiotics should survive in the intestinal tract to exert beneficial effects on the host's health. To keep a sufficient level of probiotic bacteria in the gastrointestinal tract, a shorter interval between doses may be required. Although adherence to the intestinal epithelial cell and mucus is not a universal property of probiotics, high ability to adhere to the intestinal surface might strongly interfere with infection of pathogenic bacteria and regulate the immune system. The administration of probiotic Lactobacillus stimulated indigenous Lactobacilli and the production of short‐chain fatty acids. This alteration of the intestinal environment should contribute to maintain the host's health. The immunomodulatory effects of probiotics are related to important parts of their beneficial effects. Probiotics may modulate the intestinal immune response through the stimulation of certain cytokine and IgA secretion in intestinal mucosa. The health‐beneficial effects, in particular the immunomodulation effect, of probiotics depend on the strain used. Differences in indigenous intestinal microflora significantly alter the magnitude of the effects of a probiotic. Specific probiotic strains suitable for each animal species and their life stage as well as each individual should be found.
Central L‐cysteine induces sleep, and D‐cysteine induces sleep and abnormal behavior during acute stress in neonatal chicks
Authors: YAMANE Haruka , ASECHI Mari , TSUNEYOSHI Yousuke , DENBOW D. Michael , FURUSE Mitsuhiro
Published: May 2009

L‐Cysteine (L‐Cys) is a non‐essential and glycogenic amino acid. Previously, we reported that the intracerebroventricular (i.c.v.) injection of L‐Cys induced sedative effects under isolation‐induced stress in neonatal chicks. L‐Cys has an optical isomer, D‐Cys. The aim of this study was to clarify the effect of L‐Cys and D‐Cys during a stressful condition in chicks. The i.c.v. injection of L‐Cys and D‐Cys (0.84 µmol) decreased both distress vocalization and spontaneous activity induced by isolation. However, the two cysteine isomers induced different behaviors. L‐Cys increased sleep‐like behavior while D‐Cys caused abnormal behavior including syncope as well as sleep‐like behavior. In conclusion, while both L‐Cys and D‐Cys caused a sedative effect when injected i.c.v, D‐Cys caused abnormal behavior and may be detrimental to neonatal chicks.
Increased blood concentration of isopropanol in ketotic dairy cows and isopropanol production from acetone in the rumen
Authors: SATO Hiroshi
Published: May 2009

To evaluate acetone and isopropanol metabolism in bovine ketosis, the blood concentrations of isopropanol, acetone, plasma 3‐hydroxybutyrate (3‐HB) and other metabolites were analyzed in 12 healthy controls and 15 ketotic dairy cows including fatty liver and inferior prognosis after laparotomy for displaced abomasum. In ruminal fluid taken from 6 ketotic cows, ruminal isopropanol and acetone were also analyzed. Ketotic cows showed higher concentrations of isopropanol, acetone, 3‐HB and nonesterified fatty acid, and higher activities of aspartate transaminase and γ‐glutamyl transferase than control cows. Blood samples had higher concentration of isopropanol accompanied by increased acetone. In the ketotic cows, acetone was detected not only in blood but also in ruminal fluid, while higher ruminal isopropanol did not necessarily accompany its elevation in the blood. Using 2 steers with rumen cannula, all ruminal content was emptied and then substituted with artificial saliva to evaluate the importance of ruminal microbes in isopropanol production. Under each condition of intact and emptied rumen, acetone was infused into the rumen and blood isopropanol was analyzed. The elevation in the blood isopropanol concentration after acetone infusion was markedly inhibited by the emptying. Here, increased blood concentrations of isopropanol and acetone were observed in ketotic cows, and the importance of ruminal microbes in isopropanol production was confirmed.
Nitrogen, phosphorus and potassium utilization and their cycling in a beef‐forage production system
Authors: TABATA Yusuke , TOGO Daisuke , KITAGAWA Masayuki , OISHI Kazato , KUMAGAI Hajime , KUME Shinichi , HIROOKA Hiroyuki
Published: May 2009

The objective of this study was to quantify nitrogen (N), phosphorus (P) and potassium (K) utilization and their cycling in a beef‐forage production system. A survey was conducted at the Kyoto University experimental farm in Kyoto Prefecture, Japan, and included 9.5 ha of meadow and about 160 head of beef cattle. Forages cultivated on the meadow were ensiled and offered to breeding cows. The whole farm was regarded as a beef‐forage production system. The system consisted of three components: animals, manure and soil/crop. Nutrient inputs, flows through the soil‐plant‐animal pathway and outputs were quantified for 2 periods for the whole farm. Nutrient utilization was evaluated by nutrient balances, utilization efficiencies (ratio of nutrient export to nutrient input) and cycling index. The average nutrient balances of N, P and K for the whole farm (kg/year/ha) were 435.7, 136.3, and 262.8, and the average nutrient utilization efficiencies were 0.08, 0.06, and 0.01, respectively. The characteristics of nutrient balances and utilization efficiencies for each component differed among the nutrients. The average cycling indices for N, P and K were 0.19, 0.17 and 0.49, respectively. This study illustrates the importance of internal nutrient cycling for improving nutrient utilization in beef production systems.
Immunolocalization of lingual antimicrobial peptide (LAP) in the bovine mammary gland
Authors: ISOBE Naoki , HOSODA Kenji , YOSHIMURA Yukinori
Published: May 2009

Lingual antimicrobial peptide (LAP), a member of the β‐defensin family in cows, is involved in the innate immune system and plays a crucial role in killing a large variety of microorganisms. The aim of the present study was to demonstrate the immunolocalization of LAP in the mammary glands of cows. A LAP antibody was raised in a rabbit by immunity with a synthetic 11 amino acid sequence out of a 42‐amino acid sequence of the mature form of LAP. The specificity of the LAP antibody was checked using a competitive immunoassay and Western blotting. Paraffin sections of the mammary gland were immunostained with LAP antibody. In the competitive immunoassay, an increase of synthetic LAP concentration suppressed the optical density. Western blotting analysis for LAP revealed the presence of the LAP peptide in mammary alveolar tissue. When the mammary gland was immunostained with LAP antibody, epithelial cells of both infected and non‐infected alveoli were immunopositive. These results indicate that LAP is localized in the epithelium of non‐infected as well as infected alveolus in the mammary gland in cows.
What’s in a covalent bond?
Authors: Heuts Dominic P. H. M. , Scrutton Nigel S. , McIntire William S. , Fraaije Marco W.
Published: May 2009

Many enzymes use one or more cofactors, such as biotin, heme, or flavin. These cofactors may be bound to the enzyme in a noncovalent or covalent manner. Although most flavoproteins contain a noncovalently bound flavin cofactor (FMN or FAD), a large number have these cofactors covalently linked to the polypeptide chain. Most covalent flavin–protein linkages involve a single cofactor attachment via a histidyl, tyrosyl, cysteinyl or threonyl linkage. However, some flavoproteins contain a flavin that is tethered to two amino acids. In the last decade, many studies have focused on elucidating the mechanism(s) of covalent flavin incorporation (flavinylation) and the possible role(s) of covalent protein–flavin bonds. These endeavors have revealed that covalent flavinylation is a post‐translational and self‐catalytic process. This review presents an overview of the known types of covalent flavin bonds and the proposed mechanisms and roles of covalent flavinylation.
Overexpression of human histone methylase MLL1 upon exposure to a food contaminant mycotoxin, deoxynivalenol
Authors: Ansari Khairul I. , Hussain Imran , Das Hriday K. , Mandal Subhrangsu S.
Published: May 2009

Mixed lineage leukemias (MLLs) are histone‐methylating enzymes with critical roles in gene expression, epigenetics and cancer. Although MLLs are important gene regulators little is known about their own regulation. Herein, to understand the effects of toxic stress on MLL gene regulation, we treated human cells with a common food contaminant mycotoxin, deoxynivalenol (DON). Our results demonstrate that MLLs and Hox genes are overexpressed upon exposure to DON. Studies using specific inhibitors demonstrated that Src kinase families are involved in upstream events in DON‐mediated upregulation of MLL1. Sequence analysis demonstrated that the MLL1 promoter contains multiple Sp1‐binding sites and importantly, the binding of Sp1 is enriched in the MLL1 promoter upon exposure to DON. Moreover, antisense‐mediated knockdown of Sp1 diminished DON‐induced MLL1 upregulation. These results demonstrated that MLL1 gene expression is sensitive to toxic stress and Sp1 plays crucial roles in the stress‐induced upregulation of MLL1.
Effects ofAngelicae tenuissima radix, Angelicae dahuricae radixandScutellariae radixExtracts on CytochromeP450Activities in Healthy Volunteers
Authors: Yi SoJeong , Cho Joo‐Youn , Lim Kyoung Soo , Kim Kyu‐pyo , Kim JaeWoo , Kim Bo‐Hyung , Hong Jang‐hee , Jang In‐Jin , Shin Sang‐Goo , Yu Kyung‐Sang
Published: May 2009

Abstract: Three kinds of herbal medicines, commonly used in Korea,Angelicae tenuissima radix,Angelicae dahuricae radixandScutellariae radixwere studied to evaluate their effect on cytochromeP450(CYP) activities in healthy volunteers. A total of 24 healthy male volunteers were assigned to one of three parallel herbal treatment groups, each consisting of eight volunteers. A cocktail of probe drugs for CYP enzymes was orally administered before and after multiple administrations of herbal medicines, three times a day for 13 days. Probe drugs used to measure CYP activities were caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4). The probe drugs and their metabolites were quantified in plasma or urine using HPLC or LC‐MS/MS. Changes in each CYP activity was evaluated by metabolic ratio of the probe drug (concentration ratio of metabolite to parent form at reference time point) following the herbal medication period, compared to the baseline values.A. dahuricae radixsignificantly decreased CYP1A2 activity to 10% of baseline activity (95% CI: 0.05–0.21).S. radixalso showed significant changes in CYP2C9 and CYP2E1 activities. Compared to baseline values, the metabolic activities of losartan were decreased to 71% (0.54–0.94). In addition,S. radixshowed a 1.42‐fold (1.03–1.97) increase in chlorzoxazone metabolic activity. However, CYP activities were not meaningfully influenced byA. tenuissima radix. Changes in certain CYP activities were observed after the administration ofS. radixandA. dahuricae radixin healthy volunteers. Therefore, herbal medicines containingS. radixorA. dahuricae radixare candidates for further evaluation of clinically significant CYP‐mediated herb‐drug interactions in human beings.
The Fermi blazars' divide
Authors: Ghisellini G. , Maraschi L. , Tavecchio F.
Published: May 2009

Flat-spectrum radio quasars (FSRQs) and BL Lac objects detected in the first three months of the Fermi survey neatly separate in the γ-ray spectral index versus γ-ray luminosity plane. BL Lac objects are less luminous and have harder spectra than broad-line blazars. We suggest that this division has its origin in the different accretion regimes of the two classes of objects. Using the γ-ray luminosity as a proxy for the observed bolometric one, we show that the boundary between the two subclasses of blazars can be associated with the threshold between the regimes of optically thick accretion discs and of radiatively inefficient accretion flows, which lies at an accretion rate of the order of 10−2 the Eddington rate. The spectral separation in hard (BL Lacs) and soft (FSRQs) objects can then result from the different radiative cooling suffered by the relativistic electrons in jets propagating in different ambients. We argue that the bulk of the most luminous blazars already detected by Fermi should be characterized by large black hole masses, around 109 solar masses, and predict that lowering the γ-ray flux threshold the region of the αγ–Lγ plane corresponding to steep spectral indices and lower luminosities will be progressively populated by FSRQs with lower mass black holes, while the region of hard spectra and large luminosities will remain forbidden.
Sampling Strategies for Estimation of Parameters Related to Ground Water Quality
Authors: Crane Pamela E. , Silliman Stephen E.
Published: May 2009

Multiple theoretical sampling designs are studied to determine whether sampling designs can be identified that will provide for characterization of ground water quality in rural regions of developing nations. Sampling design in this work includes assessing sampling frequency, analytical methods, length of sampling period, and requirements of sampling personnel. The results answer a set of questions regarding whether using innovative sampling designs can allow hydrogeologists to take advantage of a range of characterization technologies, sampling strategies, and available personnel to develop high‐value, water‐quality data sets. Monte Carlo studies are used to assess different sampling strategies in the estimation of three parameters related to a hypothetical chemical observed in a ground water well: mean concentration (MeanC), maximum concentration (MaxC), and total mass load (TML). Five different scenarios are simulated. These scenarios are then subsampled using multiple simulated sampling instruments, time periods (ranging from 1 to 10 years), and sampling frequencies (ranging from weekly to semiannually to parameter dependent). Results are analyzed via the statistics of the resulting estimates, including mean square error, bias, bias squared, and precision. Results suggest that developing a sampling strategy based on what may be considered lower quality instruments can represent a powerful field research approach for estimating select parameters when applied at high frequency. This result suggests the potential utility of using a combination of lower quality instrument and local populations to obtain high frequency data sets in regions where regular monitoring by technicians is not practical.
A Compartmental–Spatial System Dynamics Approach to Ground Water Modeling
Authors: Roach Jesse , Tidwell Vince
Published: May 2009

High‐resolution, spatially distributed ground water flow models can prove unsuitable for the rapid, interactive analysis that is increasingly demanded to support a participatory decision environment. To address this shortcoming, we extend the idea of multiple cell (Bear 1979) and compartmental (Campana and Simpson 1984) ground water models developed within the context of spatial system dynamics (Ahmad and Simonovic 2004) for rapid scenario analysis. We term this approach compartmental–spatial system dynamics (CSSD). The goal is to balance spatial aggregation necessary to achieve a real‐time integrative and interactive decision environment while maintaining sufficient model complexity to yield a meaningful representation of the regional ground water system. As a test case, a 51‐compartment CSSD model was built and calibrated from a 100,000+ cell MODFLOW (McDonald and Harbaugh 1988) model of the Albuquerque Basin in central New Mexico (McAda and Barroll 2002). Seventy‐seven percent of historical drawdowns predicted by the MODFLOW model were within 1 m of the corresponding CSSD estimates, and in 80% of the historical model run years the CSSD model estimates of river leakage, reservoir leakage, ground water flow to agricultural drains, and riparian evapotranspiration were within 30% of the corresponding estimates from McAda and Barroll (2002), with improved model agreement during the scenario period. Comparisons of model results demonstrate both advantages and limitations of the CCSD model approach.
Insights into the termite assemblage of a neotropical rainforest from the spatio‐temporal distribution of flying alates
Authors: BOURGUIGNON THOMAS , LEPONCE MAURICE , ROISIN YVES
Published: May 2009

Abstract. 1. During the last decade, many studies have focused on the diversity of termite species and their ecological function, but these have been mostly based on transect protocols not designed to sample canopy‐dwelling and subterranean species. Additionally, all these studies relied upon collections of foraging parties composed of workers and soldiers in the soil or in pieces of wood.

2. We hypothesised that alate‐based protocols could disclose spatial and temporal patterns of termite flights and provide a more balanced picture of assemblages for ecological and biodiversity surveys.

3. Our study took place in the framework of the IBISCA‐Panama project, which used numerous trapping methods to give a multifaceted overview of a complex tropical rainforest arthropod community. Two methods, flight interception traps and light traps, were efficient at collecting termite alates. All collected specimens were assigned to morphospecies which were later identified to the genus or species level, when possible.

4. Our results highlighted that: (i) alate trapping represents a powerful complement to ground‐based standardised sampling protocols by allowing the documentation of the whole termite assemblage. (ii) Canopy dwellers fly preferentially in the upper strata, whereas no vertical stratification was found for ground dwellers, suggesting that height of flight is dictated by a pressure for long distance dispersal as well as the need to find a suitable site for colony‐founding. (iii) Alates from closely related species do not stagger their flight period to avoid hybridisation but rather synchronise their flights according to environmental factors.
Smoking, diabetes and cardiovascular diseases in men in the Asia Pacific region
Authors: KENGNE Andre Pascal , NAKAMURA Koshi , BARZI Federica , LAM Tai Hing , HUXLEY Rachel , GU Dongfeng , PATEL Anushka , KIM Hyeon Chang , WOODWARD Mark ,   on behalf of The Asia Pacific Cohort Study Collaboration
Published: May 2009

Background:  To assess whether there is a statistical interaction between smoking and diabetes that is related to the risk of cardiovascular disease (CVD) in men in the Asia Pacific region.

Methods:  An individual participant data meta‐analysis was conducted on 34 cohort studies, involving 16 492 participants with diabetes (47.4% smokers) and 188 897 without (47.6% smokers). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for smoking (stratified by study and adjusted for age) for those with and without diabetes.

Results:  In men with diabetes, the HR (95% CI) comparing current smokers with non‐smokers was 1.42 (1.10–1.83) for coronary heart disease, 1.10 (0.88–1.37) for total stroke and 1.15 (0.98–1.35) for total CVD. The corresponding figures for men without diabetes were 1.47 (1.33–1.61), 1.27 (1.16–1.39) and 1.35 (1.27–1.44), respectively. There was no evidence of a statistical interaction between diabetes and current smoking, the number of cigarettes smoked per day or quitting smoking. Smoking cessation was associated with a 19% reduction in CVD risk, irrespective of diabetes status.

Conclusions:  The effects of cigarette smoking and smoking cessation are broadly similar in men with and without diabetes. In Asia, where there are high rates of smoking and a rapidly increasing prevalence of diabetes, strategies that encourage smokers to quit are likely to have huge benefits in terms of reducing the burden of CVD in men with diabetes.
Isolation and characterization of thirteen polymorphic microsatellite loci in the A‐genome perennial group of the legume genus Glycine
Authors: BRONSKI MICHAEL J. , STRAUB SHANNON C. K. , BOGDANOWICZ STEVEN M. , DOYLE JANE L. , BROWN A. H. D. , DOYLE JEFF J.
Published: May 2009

Thirteen polymorphic microsatellite loci were developed for the closely related and reproductively compatible species comprising the A‐genome perennial group of the legume genus Glycine. Primers developed from the widespread and isozymically differentiated G. canescens amplified successfully across G. clandestina and four other species within the complex. Species were highly polymorphic, and observed heterozygosities were extremely low for all loci, as expected for these predominantly autogamous taxa. These markers will be useful in studying genetic variation, population structure, gene flow, and polyploidy within the A‐genome group.
Characterization of microsatellite loci in the fungus, Grosmannia clavigera, a pine pathogen associated with the mountain pine beetle
Authors: TSUI C. K. M. , FEAU N. , RITLAND C. E. , MASSOUMI ALAMOUTI S. , DiGUISTINI S. , KHADEMPOUR L. , BOHLMANN J. , BREUIL C. , HAMELIN R. C.
Published: May 2009

The largest forest pest epidemic in Canadian history caused by the mountain pine beetle (MPB) and its fungal associates has killed over 15 million hectares of forest. Sixty simple sequence repeat regions were identified from Grosmannia clavigera, an MPB associated fungus. Eight loci genotyped in 53 isolates from two populations in British Columbia, Canada revealed three to 10 alleles per locus and gene diversities of 0 to 0.79. All but two of these loci showed length polymorphism in Leptographium longiclavatum, a related MPB fungal associate. These microsatellites will be useful in population genetic studies of these fungi.
Reduction of Amphotericin B-Induced Renal Tubular Apoptosis by
N
-Acetylcysteine
Authors: Odabasi Z. , Karaalp A. , Cermik H. , Mohr J. , Tigen E. T. , Koc M. , Korten V.
Published: May 2009

The reduction of amphotericin B (AmB)-induced renal tubular apoptosis and nephrotoxicity by
N
-acetylcysteine (NAC) in a murine model was evaluated. Four groups of rats were treated with AmB for 5 days, and each group concomitantly received two doses of 30, 60, or 120 mg of NAC/kg of body weight/day or sterile water for 5 days. Groups that received concomitant NAC at any dose had significantly decreased levels of apoptosis compared to that in animals receiving AmB only (48.8% versus 27.4, 23.6, or 23.5%, respectively;
P
< 0.001).
Nonsense and Missense Mutations in
FCY2
and
FCY1
Genes Are Responsible for Flucytosine Resistance and Flucytosine-Fluconazole Cross-Resistance in Clinical Isolates of
Candida lusitaniae
Authors: Florent Martine , Noël Thierry , Ruprich-Robert Gwenaël , Da Silva Bruno , Fitton-Ouhabi Valérie , Chastin Christiane , Papon Nicolas , Chapeland-Leclerc Florence
Published: May 2009

The aim of this work was to elucidate the molecular mechanisms of flucytosine (5FC) resistance and 5FC/fluconazole (FLC) cross-resistance in 11 genetically and epidemiologically unrelated clinical isolates of
Candida lusitaniae
. We first showed that the levels of transcription of the
FCY2
gene encoding purine-cytosine permease (PCP) in the isolates were similar to that in the wild-type strain, 6936. Nucleotide sequencing of the
FCY2
alleles revealed that 5FC and 5FC/FLC resistance could be correlated with a cytosine-to-thymine substitution at nucleotide 505 in the
fcy2
genes of seven clinical isolates, resulting in a nonsense mutation and in a putative nonfunctional truncated PCP of 168 amino acids. Reintroducing a
FCY2
wild-type allele at the
fcy2
locus of a
ura3
auxotrophic strain derived from the clinical isolate CL38
fcy2
(
C505T
) restored levels of susceptibility to antifungals comparable to those of the wild-type strains. In the remaining four isolates, a polymorphic nucleotide was found in
FCY1
where the nucleotide substitution T26C resulted in the amino acid replacement M9T in cytosine deaminase. Introducing this mutated allele into a 5FC- and 5FC/FLC-resistant
fcy1
Δ strain failed to restore antifungal susceptibility, while susceptibility was obtained by introducing a wild-type
FCY1
allele. We thus found a correlation between the
fcy1
T26C mutation and both 5FC and 5FC/FLC resistances. We demonstrated that only two genetic events occurred in 11 unrelated clinical isolates of
C. lusitaniae
to support 5FC and 5FC/FLC resistance: either the nonsense mutation C505T in the
fcy2
gene or the missense mutation T26C in the
fcy1
gene.
Population Pharmacokinetics of Acyclovir in Children and Young People with Malignancy after Administration of Intravenous Acyclovir or Oral Valacyclovir
Authors: Zeng L. , Nath C. E. , Blair E. Y. L. , Shaw P. J. , Stephen K. , Earl J. W. , Coakley J. C. , McLachlan A. J.
Published: May 2009

Acyclovir is effective in the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The aim of this study was to characterize the population pharmacokinetics of acyclovir observed following treatment with intravenous acyclovir and oral valacyclovir (valaciclovir) in young people with malignancy. Plasma acyclovir concentration-time data were collected from 43 patients (age range, 9 months to 20 years) who had been given multiple doses of acyclovir (5 mg/kg of body weight) and/or valacyclovir (10 mg/kg). Nonlinear mixed-effect modeling was employed to analyze acyclovir population pharmacokinetics and identify influential covariates. Simulations (
n
= 1,000) were conducted to explore the ability of the current doses to maintain acyclovir concentrations above the recommended 50% inhibitory concentration for HSV or VZV (0.56 mg/liter or 1.125 mg/liter, respectively) for more than 12 h. A one-compartment pharmacokinetic model with first-order elimination best described the acyclovir concentration-time data. The population mean estimates for clearance (CL), volume of distribution (
V
), absorption rate (

k
a

), and bioavailability (
F
) were 3.55 liters/h, 7.36 liters, 0.63 h
−1
, and 0.60, respectively. Inclusion of body weight and estimated creatinine CL (CL
CR
) in the final model reduced the interindividual variabilities in CL and
V
from 61% to 24% and from 75% to 36%, respectively. Simulations revealed that with the use of the current doses, maximal efficacy can be achieved in over 45% of patients weighing 25 to 50 kg and with CL
CR
levels of 2.0 to 4.0 liters/h/m
2
, but only in a much smaller proportion of patients, with low weights (10 kg) and high CL
CR
s (5.5 liters/h/m
2
), suggesting that higher doses are required for this subgroup. This validated population pharmacokinetic model for acyclovir may be used to develop dosing guidelines for safe and effective antiviral therapy in young people with malignancy.
Multicenter, Randomized Study of the Efficacy and Safety of Intravenous Iclaprim in Complicated Skin and Skin Structure Infections
Authors: Krievins D. , Brandt R. , Hawser S. , Hadvary P. , Islam K.
Published: May 2009

Iclaprim is a novel antibacterial agent that is currently in development for the treatment of complicated skin and skin structure infections (cSSSI). Iclaprim specifically and selectively inhibits bacterial dihydrofolate reductase, a critical enzyme in the bacterial folate pathway, and exhibits an extended spectrum of activity against various resistant pathogens, including methicillin (meticillin)-resistantStaphylococcus aureus(MRSA). The objective of this randomized, double-blind phase II study was to compare the efficacy and safety of iclaprim to those of vancomycin in patients with cSSSI. Patients were randomized to receive 0.8 mg iclaprim/kg of body weight, 1.6 mg/kg iclaprim, or 1 g vancomycin twice a day for 10 days. Clinical cure rates for the 0.8- and 1.6-mg/kg-iclaprim treatment groups were comparable to that for the vancomycin treatment group (26/28 patients [92.9%], 28/31 patients [90.3%], and 26/28 patients [92.9%], respectively). Iclaprim also showed high microbiological eradication rates. Iclaprim exhibited an eradication rate of 80% and 72% versus 59% observed with vancomycin forS. aureus, the pathogen most frequently isolated at baseline. Five MRSA cases were observed, four in the 0.8-mg/kg-iclaprim arm and one in the vancomycin arm, and all were both clinically and microbiologically cured. Iclaprim exhibited a safety profile similar to that of vancomycin, an established drug for the treatment of cSSSI. Results from this study indicate that iclaprim is a promising new therapy for the treatment of cSSSI, in particular those caused byS. aureus, including MRSA.
Noncanonical Vancomycin Resistance Cluster from
Desulfitobacterium hafniense
Y51
Authors: Kalan Lindsay , Ebert Sara , Kelly Tom , Wright Gerard D.
Published: May 2009

The glycopeptide vancomycin is a drug of last resort for infection with gram-positive organisms, and three genes are vital to resistance:
vanH
,
vanA
, and
vanX
. These genes are found in a
vanHAX
cluster, which is conserved across pathogenic bacteria, glycopeptide antibiotic producers, and other environmental bacteria. The genome sequence of the anaerobic, gram-positive, dehalogenating bacterium
Desulfitobacterium hafniense
Y51 revealed a predicted
vanA
homolog; however, it exists in a
vanAWK-murFX
cluster, unlike those of other vancomycin-resistant organisms. Using purified recombinant VanA from
D. hafniense
Y51, we determined its substrate specificity and found it to have a 42-fold preference for
d
-lactate over
d
-alanine, confirming its activity as a
d
-Ala-
d
-Lac ligase and its annotation as VanA. Furthermore, we showed that
D. hafniense
Y51 is highly resistant to vancomycin, with a MIC for growth of 64 μg/ml. Finally,

vanA
Dh

is expressed during growth in vancomycin, as demonstrated by reverse transcription-PCR. This finding represents a new glycopeptide antibiotic resistance gene cluster and expands the genetic diversity of resistance to this important class of antibiotic.
AmpDIIs Involved in Expression of the Chromosomal L1 and L2 β-Lactamases ofStenotrophomonas maltophilia
Authors: Yang Tsuey-Ching , Huang Yi-Wei , Hu Rouh-Mei , Huang Shao-Cheng , Lin Yu-Tzu
Published: May 2009

TwoampDhomologues,ampDIandampDII, ofStenotrophomonas maltophiliahave been cloned and analyzed. Comparative genomic analysis revealed that the genomic context of theampDIIgenes is quite different, whereas that of theampDIgenes is more conserved inS. maltophiliastrains. TheampDsystem ofS. maltophiliais distinct from that of theEnterobacteriaceaeandPseudomonas aeruginosain three respects. (i) AmpDIofS. maltophiliais not encoded in anampDEoperon, in contrast to what happens in theEnterobacteriaceaeandP. aeruginosa. (ii) The AmpD systems of theEnterobacteriaceaeandP. aeruginosaare generally involved in the regulation ofampR-linkedampCgene expression, while AmpDIofS. maltophiliais responsible for the regulation of two intrinsic β-lactamase genes, of which the L2 gene, but not the L1 gene, is linked toampR. (iii)S. maltophiliaexhibits a one-step L1 and L2 gene derepression model involvingampDI, distinct from the two- or three-step derepression of theEnterobacteriaceaeandP. aeruginosa. Moreover, theampDIandampDIIgenes are constitutively expressed and not regulated by the inducer and AmpR protein, and the expression ofampDIIis weaker than that ofampDI. Finally, AmpDIIis not associated with the derepression of β-lactamases, and its role inS. maltophiliaremains unclear.
Selective Upregulation of Endothelial E-Selectin in Response toHelicobacter pylori-Induced Gastritis
Authors: Svensson Helena , Hansson Malin , Kilhamn Jan , Backert Steffen , Quiding-Järbrink Marianne
Published: May 2009

Helicobacter pyloriis one of the most common bacterial pathogens, infecting up to 50% of the world's population. The host is not able to clear the infection, leading to life-long chronic inflammation with continuous infiltration of lymphocytes and granulocytes. The migration of leukocytes from the blood into inflamed tissue is dependent on adhesion molecules expressed on the vascular endothelium. The aim of this study was to characterize the effect ofH. pylori-induced gastritis with regard to the expression of endothelial adhesion molecules in the gastric mucosa and compare this to other types of chronic mucosal inflammations. Our results demonstrate an increased level of expression of the adhesion molecule E-selectin, but not of intracellular adhesion molecule 1, vascular adhesion molecule 1, or vascular adhesion protein 1, inH. pylori-induced gastritis but not in gastritis induced by acetylsalicylic acid or pouchitis. The upregulated E-selectin expression was determined to be localized to the gastric mucosa rather than being a systemic response to the infection. Moreover, theH. pyloritype IV secretion system encoded by thecagpathogenicity island (cagPAI) was found to be an important determinant for the upregulation of human endothelial E-selectin expression in vitro, and this process is probably dependent on the CagL protein, mediating binding to α5β1 integrins. Thus, endothelial E-selectin expression induced byH. pyloriprobably contributes to the large influx of neutrophils and macrophages seen in infected individuals, and our results suggest that this process may be more pronounced in patients infected withcagPAI-positiveH. pyloristrains and may thereby contribute to tissue damage in these individuals.
Advances in the diagnosis of acute pancreatitis
Authors: Rickes S , Uhle C
Published: May 2009

Early and accurate assessment of both the aetiology and the severity of acute pancreatitis enables clinicians to follow therapeutic algorithms and can result in better outcomes. Technological advances over the past decade, in particular the development of imaging modalities, have revolutionised the management of patients with acute pancreatitis. This article reviews approaches to determining the diagnosis, aetiology and severity of acute pancreatitis, with particular emphasis on new imaging techniques.
Neuroendocrine tumours of the gallbladder: three cases and a review of the literature
Authors: Iype S , Mirza T A , Propper D J , Bhattacharya S , Feakins R M , Kocher H M
Published: May 2009

Primary neuroendocrine tumours (NETs) of the gallbladder are rare. In the absence of any randomised controlled trials or prospective case series, we sought trends for clinical presentation and management based on 60 patients from published literature over the last 15 years, as well as three patients from our experience, and categorised them into various subgroups according to the WHO classification for NETs. Well-differentiated NETs have an indolent course and better prognosis. Poorly differentiated neuroendocrine carcinomas, which may be of large-cell or small-cell type and may coexist with other types of carcinoma, have a poor outcome. A variety of surgical and chemotherapeutic approaches have been adopted. Surgical excision appears to prolong life, with chemotherapy perhaps adding a marginal advantage.
Evaluation of the thyroid nodule
Authors: Ghassi D , Donato A
Published: May 2009

The annual incidence of thyroid cancer worldwide is 1 case per 100 000 men and 2.6 cases per 100 000 women. Most thyroid nodules are asymptomatic and are discovered incidentally on physical examination, self-palpation or incidentally on imaging studies performed for unrelated reasons. Although the majority of both palpable and non-palpable thyroid nodules are benign, ∼5% may represent thyroid cancer. Thyroid-stimulating hormone, thyroid ultrasound and fine-needle aspiration biopsy are key tests to guide management. Physicians caring for patients with thyroid nodules need to develop a rational, cost-effective approach to ordering and interpreting imaging and diagnostic tests in the evaluation of the thyroid nodule.