bluuebunny/crossref_metadata_2025 huggingface dataset:
Luminescence properties of Sm, Tb(Sal)3Phen complex in polyvinyl alcohol: an approach for white-light emission
Authors: Kaur Gagandeep , Rai S B
Published: October 2011

Polyvinyl alcohol polymer films doped with Sm,Tb(Sal)3Phen complexes have been synthesized using solution casting technique. An enhancement in absorption intensity is observed revealing the encapsulation of rare earth ions by salicylic acid (Sal)/1,10 phenanthroline (Phen) complex. Photoluminescence spectra of the co-doped samples were examined by varying the concentration of Tb3+ keeping concentration of Sm3+ ions fixed and vice-versa. It is found that the polymer samples emit a combination of blue, green and orange–red wavelengths tunable to white light when excited with 355 nm radiation. The emission spectra also show a self-quenching effect at higher concentration of Sm3+ ions. An efficient energy transfer was observed from Tb3+ : 5D4 → Sm3+ : 4G9/2. The reason for the enhancement in fluorescence intensities of Sm3+ in the co-doped polymer sample is the intermolecular as well as the intramolecular energy transfer.
Juvenile xanthogranuloma with lichenoid appearance
Authors: YONEDA Kozo , DEMITSU Toshio , KUBOTA Yasuo
Published: October 2011

Juvenile xanthogranulomas are benign histiocytic cell tumors that develop mainly in infancy and early childhood and then spontaneously regress. We report a 2‐year‐old boy who presented with generalized eruption of a mixture of micronodular and macronodular juvenile xanthogranuloma with a large number of widely distributed lichenoid papules. Light microscopic and immunocytochemical analyses of the lesion were consistent with juvenile xanthogranuloma. Abdominal ultrasonography did not detect any visceral lesions, and brain magnetic resonance imaging did not detect any mass lesions. We decided to observe the course without treatment in this case because there are no internal masses of juvenile xanthogranuloma. Regular follow up has therefore been scheduled. To our knowledge, this is the third report of a case demonstrating juvenile xanthogranuloma with lichenoid appearance. Future analyses of various cytokines such as granulocyte‐macrophage colony‐stimulating factor and/or tumor necrosis factor‐α in juvenile xanthogranuloma lesions should be of great help in elucidating the pathogenesis of this disease.
Identification of a phenanthrene derivative as a potent anticancer drug with Pim kinase inhibitory activity
Authors: Wang Ying‐Ying , Taniguchi Tsuyoshi , Baba Tomohisa , Li Ying‐Yi , Ishibashi Hiroyuki , Mukaida Naofumi
Published: October 2011

Pim‐3, a proto‐oncogene with serine/threonine kinase activity, is aberrantly expressed in malignant lesions, but not in normal tissues, of endoderm‐derived organs, including the pancreas, liver, colon, and stomach. Furthermore, the development of hepatocellular carcinoma is accelerated in mice expressing Pim‐3 transgene selectively in the liver when these mice are treated with a hepatocarcinogen. These observations suggest that a chemical targeting Pim‐3 kinase may be a novel type of anticancer drug. In the present study, we screened low molecular weight chemicals and observed that the phenanthrene derivative T26 potently inhibited Pim‐3 and Pim‐1, but only weakly inhibited Pim‐2. Moreover, T26 markedly inhibited the in vitro growth of human pancreatic cancer cell lines by inducing apoptosis and G2/M arrest. The growth inhibitory effects of T26 were reversed by overexpression of Pim‐3 cDNA in human pancreatic cancer cells, indicating that T26 acts primarily on Pim‐3. Furthermore, T26 inhibited the growth of a human pancreatic cancer cell line in nude mice without causing apparent adverse effects when it was administered after tumor formation was evident. These observations imply that the chemical and its related compounds may be effective for the treatment of cancers in which there is aberrant Pim‐3 expression. (Cancer Sci 2012; 103: 107–115)
Mechanism‐based population pharmacokinetic modelling in diabetes: vildagliptin as a tight binding inhibitor and substrate of dipeptidyl peptidase IV
Authors: Landersdorfer Cornelia B. , He Yan‐Ling , Jusko William J.
Published: October 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Vildagliptin is a novel antidiabetic agent that acts by inhibiting dipeptidyl peptidase IV (DPP‐4).

• DPP‐4 inhibition results in higher active concentrations of incretin hormone, glucagon‐like peptide 1 (GLP‐1), leading to reduced glucose concentrations.

• Mechanism‐based modelling of the pharmacokinetics (PK) of vildagliptin and its DPP‐4 inhibition effects in type 2 diabetic patients has not been performed.

WHAT THIS STUDY ADDS

• Population pharmacokinetic modelling of the vildagliptin concentrations from three different doses indicated the presence of a small saturable elimination pathway for vildagliptin.

• Simultaneous population modelling of the pharmacokinetics and DPP‐4 activity in patients with type 2 diabetes after treatment with vildagliptin revealed:

 1) Saturable binding of vildagliptin to DPP‐4 in plasma and tissues and partial hydrolysis of vildagliptin by DPP‐4.

 2) Vildagliptin is both an inhibitor and a substrate for DPP‐4.

AIMS To assess the pharmacokinetics of vildagliptin at different doses and build a mechanism‐based population model that simultaneously describes vildagliptin pharmacokinetics and its effects on DPP‐4 activity based on underlying physiology and biology.

METHODS Vildagliptin concentrations and DPP‐4 activity vs. time from 13 type 2 diabetic patients after oral vildagliptin 10, 25 or 100 mg and placebo twice daily for 28 days were co‐modelled. NONMEM VI and S‐ADAPT were utilized for population modelling.

RESULTS A target‐mediated drug disposition (TMDD) model accounting for capacity‐limited high affinity binding of vildagliptin to DPP‐4 in plasma and tissues had good predictive performance. Modelling the full time course of the vildagliptin‐DPP‐4 interaction suggested parallel vildagliptin dissociation from DPP‐4 by a slow first‐order process and hydrolysis by DPP‐4 to an inactive metabolite as a disposition mechanism. Due to limited amounts of DPP‐4, vildagliptin concentrations increased slightly more than dose proportionally. This newly proposed model and the parameter estimates are supported by published in vitro studies. Mean parameter estimates (inter‐individual coefficient of variation) were: non‐saturable clearance 36 l h−1 (25%), central volume of distribution 22 l (37%), half‐life of dissociation from DPP‐4 1.1 h (94%) and half‐life of hydrolysis 6.3 h (81%).

CONCLUSIONS Vildagliptin is both an inhibitor and substrate for DPP‐4. By utilizing the TMDD approach, slow dissociation of vildagliptin from DPP‐4 was found in patients and the half‐life of hydrolysis by DPP‐4 estimated. This model can be used to predict DPP‐4 inhibition effects of other dosage regimens and be modified for other DPP‐4 inhibitors to differentiate their properties.
Obesity and aspirin intolerance are risk factors for difficult‐to‐treat asthma in Japanese non‐atopic women
Authors: Fukutomi Y. , Taniguchi M. , Tsuburai T. , Tanimoto H. , Oshikata C. , Ono E. , Sekiya K. , Higashi N. , Mori A. , Hasegawa M. , Nakamura H. , Akiyama K.
Published: October 2011

Background

Asthma is a clinical syndrome characterized by variabilities in disease expression and severity. The pathophysiological mechanism underlying anti‐asthma treatment resistance is also assumed to be different between disease phenotypes.

Objective

To elucidate the effect of gender and atopic phenotype on the relationship between clinical factors and the risk of treatment resistance.

Methods

We compared outpatients with difficult‐to‐treat asthma (DTA; n = 486) in a tertiary hospital for allergic diseases in central Japan with those with controlled severe asthma (n = 621) with respect to clinical factors including body mass index (BMI) and aspirin intolerance using multivariate logistic regression analysis stratified by gender and atopic phenotype.

Results

When analysis was performed on the entire study populations, obesity (BMI ≥ 30 kg/m2; adjusted odds ratio (OR) 1.92; 95% confidence interval (95% CI: 1.07–3.43) and aspirin intolerance (OR: 2.56, 95% CI: 1.44–4.57) were found to be the significant risk factors for DTA. However, after the stratification by gender and atopic phenotype, the association between obesity and DTA was significant only in women (OR: 2.76, 95% CI: 1.31–5.78), but not in men (OR: 1.03, 95% CI: 0.38–2.81), and only in non‐atopics (OR: 4.03, 95% CI: 1.15–14.08), but not in atopics (OR: 1.54, 95% CI: 0.79–3.02). The similar gender and phenotypic differences were also observed in the association between aspirin intolerance and DTA: namely, the association was significant only in women (OR: 3.96, 95% CI: 1.84–8.50), but not in men (OR: 1.19, 95% CI: 0.46–3.05); and only in non‐atopics (OR: 5.49, 95% CI: 1.98–15.19), but not in atopics (OR: 1.39, 95% CI: 0.65–2.98).

Conclusions and Clinical Relevance

Significant associations of obesity and aspirin intolerance with DTA were observed only in women and in non‐atopics. These findings suggest that a phenotype‐specific approach is needed to treat patients with DTA.
Increased chitinase expression and fungal‐specific antibodies in the bronchoalveolar lavage fluid of asthmatic children
Authors: Goldman D. L. , Li X. , Tsirilakis K. , Andrade C. , Casadevall A. , Vicencio A. G.
Published: October 2011

Background

Increasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma.

Objective

The purpose of this study was to characterize chitinase expression and serological markers of fungal infection in children with severe asthma.

Methods

Bronchoalveolar lavage fluid (BALF) was collected from children undergoing clinically indicated flexible bronchoscopy. A diagnosis of asthma was confirmed by pulmonary function testing. BALF was tested for chitinase activity and YKL‐40 (an enzymatically inactive chitinase) concentrations. Specimens were cultured for fungal organisms and tested for cryptococcal antigen by ELISA. IgG and IgA reactivity to whole extract fungal (Aspergillus fumigatus, Alternaria alternata, Cryptococcus neoformans and Candida albicans) proteins were determined by immunoblot assay.

Results

Among the 37 patients studied, 30 were asthmatic and 7 were non‐asthmatic. Asthmatics exhibited elevated serum IgE levels (median: 748 IU/mL, IQR: 219–1765 IU/mL). Chitinase activity was greater in the BALF of asthmatics (mean, 0.85 ± 1.2 U/mL) compared with non‐asthmatics (mean: 0.23 ± 0.21 U/mL, P = 0.012). Likewise YKL‐40 concentrations were higher in the BALF of asthmatics and correlated with chitinase activity. There was a trend towards increased fungal‐specific IgG in the BALF of asthmatics compared with non‐asthmatics and for C. albicans this difference reached statistical significance. IgA reactivity to C. neoformans and A. fumigatus was greater in the BALF of asthmatics compared with non‐asthmatics.

Conclusions and Clinical Relevance

Compared with non‐asthmatics, asthmatic children exhibited increased chitinase activity and increased YKL‐40 levels in BALF. Increased IgG and IgA reactivity to fungal proteins in the BALF of asthmatics may reflect a local response to fungal infection. Our findings are consistent with and suggest a role for chitinases in asthma pathogenesis among Bronx children and provide serological evidence of an association between fungal infection and severe asthma.
Signal transducer and activation of transcription 6 (STAT6) regulates T helper type 1 (Th1) and Th17 nephritogenic immunity in experimental crescentic glomerulonephritis
Authors: Summers S A , Phoon R K S , Odobasic D , Dewage L , Kitching A R , Holdsworth S R
Published: October 2011

Experimental crescentic glomerulonephritis is driven by systemic cellular immune responses. A pathogenic role for T helper type 1 (Th1) and Th17 cells is well established. T-bet, a key transcription factor required for Th1 lineage commitment, and retinoic acid-related orphan receptor-γt (Rorγt), a key Th17 transcription factor, are required for full expression of disease. Similarly, several Th1- and Th17-associated cytokines have been implicated in disease augmentation. The role of Th2 cells in the disease is less clear, although Th2-associated cytokines, interleukin (IL)-4 and IL-10, are protective. We sought to determine the role of signal transducer and activation of transcription 6 (STAT6), a key regulator of Th2 responses, in experimental crescentic glomerulonephritis. Compared to wild-type mice, histological and functional renal injury was enhanced significantly in STAT6–/– mice 21 days after administration of sheep anti-mouse glomerular basement membrane globulin. Consistent with the enhanced renal injury, both Th1 and Th17 nephritogenic immune responses were increased in STAT6–/– mice. Conversely, production of IL-5, a key Th2-associated cytokine, was decreased significantly in STAT6–/– mice. Early in the disease process systemic mRNA expression of T-bet and Rorγ was increased in STAT6–/– mice. We conclude that STAT6 is required for attenuation of Th1 and Th17 nephritogenic immune responses and protection from crescentic glomerulonephritis.
Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene
Authors: Belforte Fiorella S. , Miras Mirta B. , Olcese María C. , Sobrero Gabriela , Testa Graciela , Muñoz Liliana , Gruñeiro‐Papendieck Laura , Chiesa Ana , González‐Sarmiento Rogelio , Targovnik Héctor M. , Rivolta Carina M.
Published: October 2011

Background  Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide resulting in hypothyroidism. Mutations in thyroid peroxidase (TPO) gene appear to be the most common cause of IOD and are commonly inherited in an autosomal recessive fashion. The TPO gene is located on the chromosome 2p25. It comprises 17 exons, covers approximately 150 kb of genomic DNA and codes 933 amino acids.

Objetives  In this study, we characterize the clinical and molecular basis of seven patients from four unrelated families with congenital hypothyroidism (CH) because of IOD.

Design and Methods  All patients underwent clinical, biochemical and imaging evaluation. The promoter and the complete coding regions of the human TPO along with the flanking intronic regions were analysed by single‐strand conformation polymorphism analysis and direct DNA sequencing. Segregation analysis of mutations was carried out, and the effect of the novel missense identified mutations was investigated by ‘in silico’ studies.

Results  All subjects had congenital and persistent primary hypothyroidism. Three novel mutations: c.796C>T [p.Q266X], c.1784G>A [p.R595K] and c.2000G>A [p.G667D] and a previously reported mutation: c.1186_1187insGGCC [p.R396fsX472] have been identified. Four patients were compound heterozygous for p.R396fsX472/p.R595K mutations, two patients were homozygous for p.R595K, and the remaining patient was a compound heterozygous for p.Q266X/p.G667D.

Conclusions  Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis.
Recurrent spontaneous hypoglycaemia causes loss of neurogenic and neuroglycopaenic signs in infants with congenital hyperinsulinism
Authors: Christesen Henrik T. , Brusgaard Klaus , Hussain Khalid
Published: October 2011

Objective  Hypoglycaemia‐associated autonomic failure (HAAF) with impaired neurogenic and neuroglycopaenic responses occurs in adults following recent, repeated hypoglycaemia. We aimed to evaluate whether HAAF also occurs in patients with infant‐onset congenital hyperinsulinism (CHI).

Design, patients  A controlled fast was performed in (i) seven CHI infants with initial symptomatic hypoglycaemia and three recent episodes of spontaneous recurrent hypoglycaemia each lasting <5 min and in (ii) seven infants with idiopathic ketotic hypoglycaemia for control.

Measurements  At the time of hypoglycaemia (blood glucose <3 mmol/l or clinical signs), blood was drawn for serum insulin, cortisol, glucagon, adrenalin and nor‐adrenalin. Signs of hypoglycaemia were documented. In CHI patients, the ABCC8 and KCNJ11 genes were analysed by denaturing high performance liquid chromatography (DHPLC) and/or direct bidirectional sequencing.

Results  Two CHI patients had a paternal ABCC8 mutation, five had no mutations. When repeated hypoglycaemia was provoked, all CHI patients exhibited a complete loss of clinical signs of hypoglycaemia, along with a global blunting of the counter‐regulatory hormones cortisol, glucagon, growth hormone, adrenalin and nor‐adrenalin responses (median values 256 nmol/l, 23 pmol/l, 5·6 mU/l, 390 pmol/l and 2·9 nmol/l, respectively), irrespective of mutational status. In the controls, hypoglycaemia was always clinically overt with normal counter‐regulatory cortisol, glucagon, adrenalin and nor‐adrenalin responses (530 nmol/l, 60, 920 pmol/l and 4·0 nmol/l, respectively).

Conclusion  Recurrent hyperinsulinaemic hypoglycaemia even of short duration blunts the autonomic, neuroglycopaenic and glucose counter‐regulatory hormonal responses in patients with infant‐onset CHI resulting in clinically silent hypoglycaemia. Tight, or continuous, glucose monitoring is therefore recommended, especially in conservatively treated patients.
Interdisciplinary approach towards female patients with Fabry disease
Authors: Weidemann Frank , Niemann Markus , Sommer Claudia , Beer Meinrad , Breunig Frank , Wanner Christoph
Published: October 2011

Eur J Clin Invest 2012; 42 (4): 455–462

Background  Fabry disease (FD) is a rare X‐linked lysosomal storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of various organs.

Design  Being X‐chromosomal‐linked, most studies in the past have focused on involvement in male patients. However, it has been elucidated recently that female patients can present typical organ involvement and thus need to be treated, respectively.

Conclusions  This review wants to give a systematical overview of the typical organ involvement in female patients with FD. Moreover, therapy recommendations especially for female patients are discussed.
Impact of electrocardiographic interpretability on outcome in patients referred for stress testing
Authors: Bouzas‐Mosquera Alberto , Peteiro Jesús , Broullón Francisco J. , Méndez Elizabet , Barge‐Caballero Gonzalo , López‐Pérez Manuel , López‐Sainz Angela , Álvarez‐García Nemesio , Castro‐Beiras Alfonso
Published: October 2011

Eur J Clin Invest 2012; 42 (5): 541–547

Background  There is limited insight into the association of electrocardiographic interpretability with outcome in patients referred for stress testing.

Methods  Exercise echocardiography was performed in 8226 patients with known or suspected coronary artery disease. Electrocardiograms were considered uninterpretable in the presence of left bundle‐branch block (LBBB), left ventricular hypertrophy (LVH) with strain, repolarization abnormalities because of digitalis therapy, ventricular paced rhythm, preexcitation or ST depression ≥ 0·1 mV because of other causes. End points were all‐cause mortality, cardiac death and hard cardiac events (i.e. cardiac death or nonfatal myocardial infarction).

Results  A total of 2450 patients had uninterpretable electrocardiograms. During a follow‐up period of 4·1 ± 3·5 years, there were 1011 deaths (of which 478 were cardiac deaths) and 1069 patients experienced a hard cardiac event. The 5‐year rates of death, cardiac death and hard cardiac events were, respectively, 18·7%, 10·9% and 18·8% in patients with uninterpretable ECGs, compared with 9·5%, 4·1% and 10·9% in those with interpretable ECGs (P < 0·001). After covariate adjustment, lack of ECG interpretability remained an independent predictor of all‐cause mortality (hazard ratio [HR] 1·25, 95% confidence interval [CI] 1·08–1·44, P = 0·002), cardiac death (HR 1·63, 95% CI 1·32–2·01, P < 0·001) and hard cardiac events (HR 1·28, 95% CI 1·11–1·47, P < 0·001). When the specific ECG abnormalities were included as covariates, LBBB, LVH and digitalis therapy remained predictors of cardiac death; LBBB and LVH were predictors of hard cardiac events, and LVH remained predictive of all‐cause mortality.

Conclusion  Uninterpretable ECGs portend a worse prognosis in patients referred for stress testing.
Influence of an ecosystem engineer, the emergent macrophyte Sparganium erectum, on seed trapping in lowland rivers and consequences for landform colonisation
Authors: O’HARE JUDITH M. , O’HARE MATTHEW T. , GURNELL ANGELA M. , SCARLETT PETER M. , LIFFEN TOM , McDONALD CLAIRE
Published: October 2011

1. Plant physical ecosystem engineers can influence vegetation population and community dynamics by modifying, maintaining or creating habitats. They may also have the potential to act upon biotic processes, such as seed dispersal.

2. Examples exist of reduction in seed dispersal distances in vegetated compared to unvegetated terrestrial environments, and concentration of seed deposits associated with plant patches. Such effects in aquatic environments have been little studied, but the engineering effect of plant patches on patterns of flow velocity and sediment deposition in streams suggests that they may play a similar role.

3. In this study, we assess the potential of an emergent aquatic species, Sparganium erectum, to play a role in physically modifying river habitats and trapping seeds by examining patterns of seed deposition and substrate type in 47 river reaches across England and southern Scotland, U.K.

4. Areas of the river channel within or adjacent to S. erectum patches harboured more plant seeds and more species than unvegetated areas and had finer, sandier substrates with higher organic matter, total nitrogen and total phosphorus content. Most seed species were competitive, indicating that they were well suited to colonise the competitive environment of an S. erectum patch, and could potentially further stabilise accumulated sediments and contribute to landform development.

5. We demonstrate that S. erectum patches influence both the physical environment and the retention of seeds, in consistent patterns across the channel bed, for a range of lowland rivers that vary in stream power and geology and which can be expected to vary in levels of supply of fine sediment and seeds.

6. Our findings support the hypothesis that the fundamental influence of a riverine ecosystem‐engineering species on slowing fluid flow links the habitat creation process of sediment sorting and retention to seed trapping. We suggest the process is applicable to a wide range of aquatic and riparian vegetation. We also suggest that the mono‐specific and competitive growth, which is typical of these engineering species, will strongly influence the recruitment of trapped seeds.
A relationship between metabolic rate and risk‐taking behaviour is revealed during hypoxia in juvenile European sea bass
Authors: Killen Shaun S. , Marras Stefano , Ryan Mary R. , Domenici Paolo , McKenzie David J.
Published: October 2011

1. Inter‐individual variation in metabolic rate exists in a wide range of taxa. While this variation appears to be linked to numerous aspects of animal behaviour and personality, the ecological relevance of these relationships is not understood. The behavioural response of individual fish to acute aquatic hypoxia, for example, could be related to metabolic rate via influences on oxygen demand or the willingness to take risks. Individuals with higher metabolic rates could show greater hypoxia‐associated increases in activity that could allow them to locate areas with increased oxygen availability but that also make them susceptible to predation. Any relationship between metabolic rate and risk‐taking behaviour among individual fish could therefore be modulated by environmental oxygen levels, perhaps becoming stronger as oxygen availability declines.

2. We measured spontaneous swimming activity as an index of risk‐taking by juvenile European sea bass in normoxia, moderate hypoxia (40% air saturation) and severe hypoxia (20% air saturation) after being startled by a predator model. All fish were also separately measured for routine metabolic rate by measuring oxygen uptake.

3. In hypoxia, fish re‐emerged from cover sooner after a simulated attack and were generally more active than when the same fish were startled in normoxia. In addition, individual activity and risk‐taking in severe hypoxia were positively correlated with metabolic rate. Aquatic surface respiration was a major contributor towards increased activity in hypoxia and was positively related to metabolic rate during severe hypoxia. There were no relationships between risk‐taking and metabolic rate in moderate hypoxia or normoxia.

4. Relative measures of risk‐taking among individual fish were not consistent among oxygen levels, further suggesting that individuals differ in sensitivity to hypoxia and the degree to which this environmental stressor affects risk‐taking behaviour.

5. These results suggest that fish with relatively high metabolic rates become more active during acute hypoxia, possibly leading to increased susceptibility to predation in response to differences in metabolic demand. In addition, the relationship between metabolic rate and risk‐taking may only be observable during exposure to a physiological stressor or such a stressor may strengthen any relationships observable under more benign conditions.
Arctic warming on two continents has consistent negative effects on lichen diversity and mixed effects on bryophyte diversity
Authors: Lang Simone I. , Cornelissen Johannes H. C. , Shaver Gaius R. , Ahrens Matthias , Callaghan Terry V. , Molau Ulf , Ter Braak Cajo J. F. , Hölzer Adam , Aerts Rien
Published: October 2011

Little is known about the impact of changing temperature regimes on composition and diversity of cryptogam communities in the Arctic and Subarctic, despite the well‐known importance of lichens and bryophytes to the functioning and climate feedbacks of northern ecosystems. We investigated changes in diversity and abundance of lichens and bryophytes within long‐term (9–16 years) warming experiments and along natural climatic gradients, ranging from Swedish subarctic birch forest and subarctic/subalpine tundra to Alaskan arctic tussock tundra. In both Sweden and Alaska, lichen diversity responded negatively to experimental warming (with the exception of a birch forest) and to higher temperatures along climatic gradients. Bryophytes were less sensitive to experimental warming than lichens, but depending on the length of the gradient, bryophyte diversity decreased both with increasing temperatures and at extremely low temperatures. Among bryophytes, Sphagnum mosses were particularly resistant to experimental warming in terms of both abundance and diversity. Temperature, on both continents, was the main driver of species composition within experiments and along gradients, with the exception of the Swedish subarctic birch forest where amount of litter constituted the best explanatory variable. In a warming experiment in moist acidic tussock tundra in Alaska, temperature together with soil ammonium availability were the most important factors influencing species composition. Overall, dwarf shrub abundance (deciduous and evergreen) was positively related to warming but so were the bryophytes Sphagnum girgensohnii, Hylocomium splendens and Pleurozium schreberi; the majority of other cryptogams showed a negative relationship to warming. This unique combination of intercontinental comparison, natural gradient studies and experimental studies shows that cryptogam diversity and abundance, especially within lichens, is likely to decrease under arctic climate warming. Given the many ecosystem processes affected by cryptogams in high latitudes (e.g. carbon sequestration, N2‐fixation, trophic interactions), these changes will have important feedback consequences for ecosystem functions and climate.
Changing growth response to wildfire in old‐growth ponderosa pine trees in montane forests of north centralIdaho
Authors: Keeling Eric G. , Sala Anna
Published: October 2011

NorthAmerican fire‐adapted forests are experiencing changes in fire frequency and climate. These novel conditions may alter postwildfire responses of fire‐adapted trees that survive fires, a topic that has received little attention. Historical, frequent, low‐intensity wildfire in many fire‐adapted forests is generally thought to have a positive effect on the growth and vigor of trees that survive fires. Whether such positive effects can persist under current and future climate conditions is not known. Here, we evaluate long‐term responses to recurrent 20th‐century fires in ponderosa pine, a fire‐adapted tree species, in unlogged forests in north centralIdaho. We also examine short‐term responses to individual 20th‐century fires and evaluate whether these responses have changed over time and whether potential variability relates to climate variables and time since last fire. Growth responses were assessed by comparing tree‐ring measurements from trees in stands burned repeatedly during the 20th century at roughly the historical fire frequency with trees in paired control stands that had not burned for at least 70 years. Contrary to expectations, only one site showed significant increases in long‐term growth responses in burned stands compared with control stands. Short‐term responses showed a trend of increasing negative effects of wildfire (reduced diameter growth in the burned stand compared with the control stand) in recent years that had drier winters and springs. There was no effect of time since the previous fire on growth responses to fire. The possible relationships of novel climate conditions with negative tree growth responses in trees that survive fire are discussed. A trend of negative growth responses to wildfire in old‐growth forests could have important ramifications for forest productivity and carbon balance under future climate scenarios.
Radiative forcing of natural forest disturbances
Authors: O'Halloran Thomas L. , Law Beverly E. , Goulden Michael L. , Wang Zhuosen , Barr Jordan G. , Schaaf Crystal , Brown Mathew , Fuentes José D. , Göckede Mathias , Black Andrew , Engel Vic
Published: October 2011

Forest disturbances are major sources of carbon dioxide to the atmosphere, and therefore impact global climate. Biogeophysical attributes, such as surface albedo (reflectivity), further control the climate‐regulating properties of forests. Using both tower‐based and remotely sensed data sets, we show that natural disturbances from wildfire, beetle outbreaks, and hurricane wind throw can significantly alter surface albedo, and the associated radiative forcing either offsets or enhances the CO2 forcing caused by reducing ecosystem carbon sequestration over multiple years. In the examined cases, the radiative forcing from albedo change is on the same order of magnitude as the CO2 forcing. The net radiative forcing resulting from these two factors leads to a local heating effect in a hurricane‐damaged mangrove forest in the subtropics, and a cooling effect following wildfire and mountain pine beetle attack in boreal forests with winter snow. Although natural forest disturbances currently represent less than half of gross forest cover loss, that area will probably increase in the future under climate change, making it imperative to represent these processes accurately in global climate models.
T‐cell‐inducing vaccines – what’s the future
Authors: Gilbert Sarah C.
Published: October 2011

In the twentieth century vaccine development has moved from the use of attenuated or killed micro‐organisms to protein sub‐unit vaccines, with vaccine immunogenicity assessed by measuring antibodies induced by vaccination. However, for many infectious diseases T cells are an important part of naturally acquired protective immune responses, and inducing these by vaccination has been the aim of much research. The progress that has been made in developing effective T‐cell‐inducing vaccines against viral and parasitic diseases such as HIV and malaria is discussed, along with recent developments in therapeutic vaccine development for chronic viral infections and cancer. Although many ways of inducing T cells by vaccination have been assessed, the majority result in low level, non‐protective responses. Sufficient clinical research has now been conducted to establish that replication‐deficient viral vectored vaccines lead the field in inducing strong and broad responses, and efficacy studies of T‐cell‐inducing vaccines against a number of diseases are finally demonstrating that this is a valid approach to filling the gaps in our defence against not only infectious disease, but some forms of cancer.
MHC class I dimer formation by alteration of the cellular redox environment and induction of apoptosis
Authors: Makhadiyeva Dinara , Lam Lorraine , Moatari Mohammad , Vallance Jasmine , Zheng Ying , Campbell Elaine C. , Powis Simon J.
Published: October 2011

Many MHC class I molecules contain unpaired cysteine residues in their cytoplasmic tail domains, the function of which remains relatively uncharacterized. Recently, it has been shown that in the small secretory vesicles known as exosomes, fully folded MHC class I dimers can form through a disulphide bond between the cytoplasmic tail domain cysteines, induced by the low levels of glutathione in these extracellular vesicles. Here we address whether similar MHC class I dimers form in whole cells by alteration of the redox environment. Treatment of the HLA‐B27‐expressing Epstein–Barr virus‐transformed B‐cell line Jesthom, and the leukaemic T‐cell line CEM transfected with HLA‐B27 with the strong oxidant diamide, and the apoptosis‐inducing and glutathione‐depleting agents hydrogen peroxide and thimerosal, induced MHC class I dimers. Furthermore, induction of apoptosis by cross‐linking FasR/CD95 on CEM cells with monoclonal antibody CH‐11 also induced MHC class I dimers. As with exosomal MHC class I dimers, the formation of these structures on cells is controlled by the cysteine at position 325 in the cytoplasmic tail domain of HLA‐B27. Therefore, the redox environment of cells intimately controls induction of MHC class I dimers, the formation of which may provide novel structures for recognition by the immune system.
Inter‐oceanic variation in patterns of host‐associated divergence in a seabird ectoparasite
Authors: Dietrich Muriel , Kempf Florent , Gómez‐Díaz Elena , Kitaysky Alexander S. , Hipfner J. Mark , Boulinier Thierry , McCoy Karen D.
Published: October 2011

Aim  Parasites with global distributions and wide host spectra provide excellent models for exploring the factors that drive parasite diversification. Here, we tested the relative force of host and geography in shaping population structure of a widely distributed and common ectoparasite of colonial seabirds, the tick Ixodes uriae.

Location  Two natural geographic replicates of the system: numerous seabird colonies of the North Pacific and North Atlantic Ocean basins.

Methods  Using eight microsatellite markers and tick samples from a suite of multi‐specific seabird colonies, we examined tick population structure in the North Pacific and compare patterns of diversity and structure to those in the Atlantic basin. Analyses included population genetic estimations of diversity and population differentiation, exploratory multivariate analyses, and Bayesian clustering approaches. These different analyses explicitly took into account both the geographic distance among colonies and host use by the tick.

Results  Overall, little geographic structure was observed among Pacific tick populations. However, host‐related genetic differentiation was evident, but was variable among host types and lower than in the North Atlantic.

Main conclusions  Tick population structure is concordant with the genetic structure observed in seabird host species within each ocean basin, where seabird populations tend to be less structured in the North Pacific than in the North Atlantic. Reduced tick genetic structure in the North Pacific suggests that host movement among colonies, and thus tick dispersal, is higher in this region. In addition to information on parasite diversity and gene flow, our findings raise interesting questions about the subtle ways that host behaviour, distribution and phylogeographic history shape the genetics of associated parasites across geographic landscapes.
Metagenetic community analysis of microbial eukaryotes illuminates biogeographic patterns in deep‐sea and shallow water sediments
Authors: BIK HOLLY M. , SUNG WAY , DE LEY PAUL , BALDWIN JAMES G. , SHARMA JYOTSNA , ROCHA‐OLIVARES AXAYÁCATL , THOMAS W. KELLEY
Published: October 2011

Microbial eukaryotes (nematodes, protists, fungi, etc., loosely referred to as meiofauna) are ubiquitous in marine sediments and probably play pivotal roles in maintaining ecosystem function. Although the deep‐sea benthos represents one of the world’s largest habitats, we lack a firm understanding of the biodiversity and community interactions amongst meiobenthic organisms in this ecosystem. Within this vast environment, key questions concerning the historical genetic structure of species remain a mystery, yet have profound implications for our understanding of global biodiversity and how we perceive and mitigate the impact of environmental change and anthropogenic disturbance. Using a metagenetic approach, we present an assessment of microbial eukaryote communities across depth (shallow water to abyssal) and ocean basins (deep‐sea Pacific and Atlantic). Within the 12 sites examined, our results suggest that some taxa can maintain eurybathic ranges and cosmopolitan deep‐sea distributions, but the majority of species appear to be regionally restricted. For Operationally Clustered Taxonomic Units (OCTUs) reporting wide distributions, there appears to be a taxonomic bias towards a small subset of taxa in most phyla; such bias may be driven by specific life history traits amongst these organisms. In addition, low genetic divergence between geographically disparate deep‐sea sites suggests either a shorter coalescence time between deep‐sea regions or slower rates of evolution across this vast oceanic ecosystem. While high‐throughput studies allow for broad assessment of genetic patterns across microbial eukaryote communities, intragenomic variation in rRNA gene copies and the patchy coverage of reference databases currently present substantial challenges for robust taxonomic interpretations of eukaryotic data sets.
Determining sites of interaction between prenisin and its modification enzymes NisB and NisC
Authors: Khusainov Rustem , Heils René , Lubelski Jacek , Moll Gert N. , Kuipers Oscar P.
Published: October 2011

Although nisin is a model lantibiotic, our knowledge of the specific interactions of prenisin with its modification enzymes remains fragmentary. Here, we demonstrate that the nisin modification enzymes NisB and NisC can be pulled down in vitro from Lactococcus lactis by an engineered His‐tagged prenisin. This approach enables us to determine important intermolecular interactions of prenisin with its modification machinery within L. lactis. We demonstrate that (i) NisB has stronger interactions with precursor nisin than NisC has, (ii) deletion of the propeptide part keeping the nisin leader intact leads to a lack of binding, (iii) NisB point mutants of highly conserved residues W616, F342A, Y346F and P639A are still able to dehydrate prenisin, (iv) NisB Δ(77–79)Y80F mutant decreased the levels of NisB–prenisin interactions and resulted in unmodified prenisin, (v) substitution of an active site residue H331A in NisC leads to higher amounts of the co‐purified complex, (vi) NisB is present in the form of a dimer, and (vii) the region FNLD (‐18 to ‐15) of the leader is an important site for binding not only to NisB, but also to NisC.
Stressful events, smoking exposure and other maternal risk factors associated with gestational diabetes mellitus
Authors: Hosler Akiko S. , Nayak Seema G. , Radigan Anne M.
Published: October 2011

Hosler AS, Nayak SG, Radigan AM. Stressful events, smoking exposure and other maternal risk factors associated with gestational diabetes mellitus. Paediatric and Perinatal Epidemiology 2011; 25: 566–574.

The incidence of gestational diabetes mellitus (GDM) has increased significantly in the last few decades in the US. Understanding its risk factors is imperative for the prevention of GDM and its sequelae, but the roles of behavioural risk factors such as stressful events and smoking on GDM are generally not well understood. Using data obtained from the New York State (NYS) Pregnancy Risk Assessment Monitoring System survey for 2004–06 and the NYS birth certificates, we examined relationships between GDM, stressful events and smoking among 2690 women who had live singleton births and did not have pre‐pregnancy diabetes.

After adjustment for risk factors such as maternal age, race/ethnicity, pre‐pregnancy body mass index, hypertension, as well as smoking exposure, education, parity, and gestation at first visit for prenatal care, we found that having five or more stressful events 12 months before the baby was born was significantly associated with GDM (OR = 2.49, [95% CI 1.49, 4.16]). In another model, having any stressful event(s) other than ‘moved to a new address’ 12 months before the baby was born was also moderately associated with GDM (OR = 1.38, [95% CI 1.04, 1.85]). Smoking exposure, assessed by combining maternal smoking and second‐hand smoke exposure into six levels, had no significant association with GDM, and did not show a dose–response pattern.

The present study suggests that stressful events during pregnancy may be an independent risk factor for GDM. Future studies of GDM should include this common, but potentially modifiable risk factor in analyses.
Phytophthora obscura sp. nov., a new species of the novel Phytophthora subclade 8d
Authors: Grünwald N. J. , Werres S. , Goss E. M. , Taylor C. R. , Fieland V. J.
Published: October 2011

A new Phytophthora species was detected (i) in the USA, infecting foliage of Kalmia latifolia, (ii) in substrate underneath Pieris, and (iii) in Germany in soil samples underneath Aesculus hippocastanum showing disease symptoms. The new species Phytophthora obscura sp. nov. is formally named based on phylogenetic analysis, host range, Koch’s postulates and morphology. Phytophthora obscura is homothallic with paragynous antheridia and semipapillate sporangia. It is genetically closely related to P. syringae and P. austrocedrae and together these three species define a new Phytophthora subclade 8d, with significant support for all genetic loci analysed including seven nuclear genes and the mitochondrial gene coxII. The morphological and ecological characteristics are very similar to P. syringae, and it is likely that P. obscura was not described earlier because it was identified as P. syringae. Artificial inoculations indicated that horse chestnut, kalmia, pieris and rhododendron might be hosts, and Koch’s postulates were confirmed for kalmia from which it was isolated. This pathogen was named after its elusive nature since it has to date rarely been detected in the US and Germany.
Petrology and geochemistry of chert on the marginal zone of Yangtze Platform, western Hunan, South China, during the Ediacaran–Cambrian transition
Authors: WANG JIANGUO , CHEN DAIZHAO , WANG DAN , YAN DETIAN , ZHOU XIQIANG , WANG QINGCHEN
Published: October 2011

The Ediacaran–Cambrian transition was one of the most critical intervals in Earth history. During this interval, widespread chert was precipitated, commonly as a stratal wedge in carbonates, along the southern margin of the Yangtze Platform, South China. The chert wedge passes into a full chert succession further basinward to the south‐east. Four lithotypes of chert are identified across the marginal zone in western Hunan: mounded, vein, brecciated and bedded chert. The mounded chert is characterized by irregular to digitiform internal fabrics, generally with abundant original vesicles and/or channels that mostly are lined by botryoidal chalcedony cements with minor quartz and barite crystals. The host chert (or matrix) of these mounds is dominated by amorphous cryptocrystalline silica, commonly disseminated with pyrite. The vein chert, with minor quartz locally, generally cross‐cuts the overlying dolostone and chert horizons and terminates under the mounded and/or bedded chert bodies. The brecciated chert commonly occurs as splayed ‘intrusions’ or funnel‐shaped wedges and cross‐cuts the topmost dolostones. The bedded chert, the most common type, generally is thin to medium‐bedded and laminated locally; it is composed of amorphous silica with minor amounts of black lumps. Microthermometry of fluid inclusions from vein and void‐lining minerals (mainly quartz and barite) revealed homogenization temperatures from 120 to 180°C for the trapped primary fluids. Compositionally, these chert deposits generally are pure, with SiO2 > 92 wt%, and only minor Fe2O3 and Al2O3 contents, most of which show positive Europium anomalies in rare earth element patterns, especially for the mounded chert. All these data suggest that the marginal zone chert deposits resulted from a low‐temperature, silica‐rich hydrothermal system, in which the mounded chert was precipitated around the releasing vents, i.e. as silica chimneys. The vein and splayed brecciated chert, however, was formed along the syndepositional fault/fracture conduits that linked downward, while the bedded chert was precipitated in the quieter water column from the fallout of hydrothermal plumes onto the sea floor. These petrological and geochemical data provide compelling evidence and a new clue to the understanding of the extensive silica precipitation; rapid tectono‐depositional and oceanic changes during the Ediacaran–Cambrian transition in South China.
Clinical study on prevention of HBV re‐infection by entecavir after liver transplantation
Authors: Cai Chang‐jie , Lu Min‐qiang , Chen Ying‐hua , Zhao Hui , Li Min‐ru , Chen Gui‐hua
Published: October 2011

Cai C‐j, Lu M‐q, Chen Y‐h, Zhao H, Li M‐r, Chen G‐h. Clinical study on prevention of HBV re‐infection by entecavir after liver transplantation.  Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01448.x.  © 2011 John Wiley & Sons A/S.

Abstract:  Purpose:  This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re‐infection after liver transplantation (LT).

Methods:  A retrospective matched case‐control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected.

Results:  Two hundred and fifty‐two patients were enrolled. The average duration of follow‐up was 38.5 and 41.2 months (LAM and ETV groups) (p > 0.05). Duration of pre‐operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p > 0.05). The HBV DNA level decreased from 3.89 × 106 to 5.31 × 105 copies/mL before LT in the LAM group, and decreased from 8.74 × 106 to 5.49 × 104 copies/mL in the ETV group (p < 0.05). Eighteen patients in LAM group developed HBV re‐infection and 0 in ETV group.

Conclusion:  ETV is superior to LAM for preventing HBV re‐infection following LT.