bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SummaryBackgroundIncreasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma.ObjectiveThe purpose of this study was to characterize chitinase expression and serological markers of fungal infection in children with severe asthma.MethodsBronchoalveolar 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.ResultsAmong 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 RelevanceCompared 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

Summary
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

SummaryBackground  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

SummaryObjective  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): 455–462AbstractBackground  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): 541–547AbstractBackground  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

Summary1. 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

Summary1. 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

AbstractLittle 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

AbstractNorthAmerican 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

AbstractForest 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

SummaryIn 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.