bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolism, nitrogen excretion, and heat shock proteins in the central mudminnow (Umbra limi), a facultative air-breathing fish living in a variable environment
Authors: Currie S. , Bagatto B. , DeMille M. , Learner A. , LeBlanc D. , Marks C. , Ong K. , Parker J. , Templeman N. , Tufts B. L. , Wright P. A. 
Published: January 2010

The central mudminnow ( Umbra limi (Kirtland, 1841)) is a continuous, facultative air-breathing freshwater fish found in swamps of central Canada and northeastern USA. The first goal of this field and laboratory-based study was to characterize the physicochemical conditions of mudminnow habitat during the summer. Our second goal was to determine the metabolic, stress response, and nitrogen excretion strategies of this fish following variations in water temperature, dissolved oxygen, external ammonia, and short-term periods of air exposure. We report profound diurnal fluctuations in water temperature (13–31 °C), dissolved oxygen (2%–159% air saturation), and ammonia levels (10–240 μmol·L−1) in habitat of central mudminnow measured on three dates at six different sites over 24 h. The central mudminnow does not induce urea synthesis as a mechanism of ammonia detoxification, either in response to emersion (6 or 20 h) or elevated external ammonia (10 mmol·L–1). Acute exposure to high temperature (~31 °C), aquatic hypoxia, or air resulted in significant increases in blood glucose and liver heat shock protein (Hsp) 70 and hypoxia also caused an increased reliance on anaerobic metabolism. This is the first description of the heat shock response in a facultative air-breathing fish following either hypoxia or air exposure. These metabolic and molecular responses are part of a strategy that allows the mudminnow to thrive in extremely variable freshwater environments.
Risk perception of nesting Great Blue Herons: experimental evidence of habituation
Authors: Vennesland Ross G. 
Published: January 2010

The nesting behaviour of the Great Blue Heron ( Ardea herodias L., 1758) was studied in western Canada in 1998 and 1999 to (i) investigate how individual parents assess risk when repeatedly exposed to a disturbance stimulus (an investigator) and (ii) experimentally test in the field whether any variation in their nest defense behaviour was due to experience with the disturbance stimuli or the stage of the nesting period. Heron response declined through the nesting period and the level of response varied among colonies, suggesting different perceptions of risk among groups of herons in the study. It was experimentally shown that variation in the response of herons through one nesting period was due to both behavioural habituation and the stage of the nesting period. Response was stronger in 1999 than in 1998, indicating that habituation did not hold between nesting periods. In general, habituation in herons may bode well for their potential to persist in areas with light human use. But irrespective of habituation, stimuli early in the nesting period and large or novel events may still cause herons to abandon their nests owing to the effects of the stage of the nesting period.
Honeydew and nectar sugars differentially affect flight performance in female black flies
Authors: Stanfield T. K. , Hunter F. F. 
Published: January 2010

In the wild, black flies (Diptera: Simuliidae) feed on both floral nectar and homopteran honeydew. We tested the hypothesis that sugar meal composition affects flight performance using tethered black flies that had been flown to exhaustion. Individuals were then fed distilled water (dH2O), 10% (m/v) artificial nectar (AN), or 20% (m/v) artificial honeydew (AH) sugars, and the distance, speed, and duration of the resultant flights were recorded using a computerized flight mill. Following a dH2O meal, flies were unable to regain flight. There were three different artificial honeydew diets (AHlow, AHmed, AHhigh), each differing in the proportion and composition of simple sugars (glucose, fructose, sucrose) and complex sugars (melezitose, stachyose). Flies flew the farthest and longest on AH meals that contained higher levels of complex sugars (AHmed, AHhigh) compared with flies fed on AN (simple sugars only) or AHlow. On this flight mill, the mean flight speed was 10.6 ± 3.5 m/min and was not affected by the type of sugar meal ingested.
Increased Coupled Gating of L-Type Ca2+Channels During Hypertension and Timothy Syndrome
Authors: Navedo Manuel F. , Cheng Edward P. , Yuan Can , Votaw Scott , Molkentin Jeffery D. , Scott John D. , Santana Luis F. 
Published: January 2010

Rationale:L-Type (Cav1.2) Ca2+channels are critical regulators of muscle and neural function. Although Cav1.2 channel activity varies regionally, little is known about the mechanisms underlying this heterogeneity.Objective:To test the hypothesis that Cav1.2 channels can gate coordinately.Methods and Results:We used optical and electrophysiological approaches to record Cav1.2 channel activity in cardiac, smooth muscle, and tsA-201 cells expressing Cav1.2 channels. Consistent with our hypothesis, we found that small clusters of Cav1.2 channels can open and close in tandem. Fluorescence resonance energy transfer and electrophysiological studies suggest that this coupling of Cav1.2 channels involves transient interactions between neighboring channels via their C termini. The frequency of coupled gating events increases in hypertensive smooth muscle and in cells expressing a mutant Cav1.2 channel that causes arrhythmias and autism in humans with Timothy syndrome (LQT8).Conclusions:Coupled gating of Cav1.2 channels may represent a novel mechanism for the regulation of Ca2+influx and excitability in neurons, cardiac, and arterial smooth muscle under physiological and pathological conditions.
Anterior Cruciate Ligament—Deficient Potential Copers and Noncopers Reveal Different Isokinetic Quadriceps Strength Profiles in the Early Stage after Injury
Authors: Eitzen Ingrid , Eitzen Thomas J. , Holm Inger , Snyder-Mackler Lynn , Risberg May Arna 
Published: January 2010

Background Isokinetic muscle strength testing using the peak torque value is the most frequently included quadriceps muscle strength measurement for anterior cruciate ligament (ACL)—injured subjects. Purpose and Hypotheses The purpose of this study was to investigate quadriceps muscle performance during the whole isokinetic curve in subjects with ACL deficiency classified as potential copers or noncopers and to investigate whether these curve profiles were associated with single-legged hop performance. We hypothesized that quadriceps muscle torque at other knee flexion angles than peak torque would give more information about quadriceps muscle strength deficits. Furthermore, we hypothesized that there would be significant torque differences between potential copers and noncopers and a significant relationship between angle-specific torque values and single-legged hop performance. Study Design Cross-sectional study; Level of evidence, 3. Methods Seventy-six individuals with a complete unilateral ACL rupture within the last 3 months were included. The subjects were classified as potential copers and noncopers. Isokinetic quadriceps muscle tests were performed at 60 deg/s. Mean torque values were calculated for peak torque as well as for specific knee flexion angles. The 1-legged hop and the 6-m timed hop tests were included, and symmetry indices were used. Results The peak torque value did not identify the largest quadriceps muscle strength deficit. Rather, these were established at knee flexion angles of less than 40°. There were significant differences in angle-specific torque values between potential copers and noncopers (P < .05). Moderate to strong associations were disclosed between angle-specific torque values and single-legged hop performance, but only for noncopers (r ≥ .32-.58). Conclusion Angle-specific quadriceps muscle torque values of less than 40° of knee flexion provide more information on the quadriceps strength deficits after ACL injury than the commonly used peak torque values. Interpretation of the isokinetic curve profiles seems to be of clinical importance for the evaluation of quadriceps muscle performance after ACL injury.
An in vivo model to study and manipulate the hematopoietic stem cell niche
Authors: Song Junhui , Kiel Mark J. , Wang Zhou , Wang Jingcheng , Taichman Russell S. , Morrison Sean J. , Krebsbach Paul H. 
Published: January 2010

AbstractBecause the microenvironment that supports hematopoietic stem cell (HSC) proliferation and differentiation is not fully understood, we adapted a heterotopic bone formation model as a new approach for studying the HSC microenvironment in vivo. Endogenous HSCs homed to tissue-engineered ossicles and individually sorted HSCs from ossicles were able to reconstitute lethally irradiated mice. To further explore this model as a system to study the stem cell niche, ossicles were established with or without anabolic parathyroid hormone (PTH) treatment during the 4-week course of bone development. Histology and micro–computed tomography showed higher bone area-to-total area ratios, thicker cortical bone and trabecular bone, significantly higher bone mineral density and bone volume fraction in PTH-treated groups than in controls. By an in vivo competitive long-term reconstitution assay, HSC frequency in the ossicle marrow was 3 times greater in PTH groups than in controls. When whole bone marrow cells were directly injected into the ossicles after lethal irradiation, the PTH-treated groups showed an enhanced reconstitution rate compared with controls. These findings suggest the residence of HSCs in heterotopic bone marrow and support the future use of this ossicle model in elucidating the composition and regulation of the HSC niche.
Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation
Authors: Micklethwaite Kenneth P. , Savoldo Barbara , Hanley Patrick J. , Leen Ann M. , Demmler-Harrison Gail J. , Cooper Laurence J. N. , Liu Hao , Gee Adrian P. , Shpall Elizabeth J. , Rooney Cliona M. , Heslop Helen E. , Brenner Malcolm K. , Bollard Catherine M. , Dotti Gianpietro 
Published: January 2010

AbstractViral infections and leukemic relapse account for the majority of treatment failures in patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving allogeneic hematopoietic stem cell (HSC) or cord blood (CB) transplants. Adoptive transfer of virus-specific cytotoxic T lymphocytes (CTLs) provides protection against common viruses causing serious infections after HSC transplantation without concomitant graft-versus-host disease. We have now generated CTL lines from peripheral blood (PB) or CB units that recognize multiple common viruses and provide antileukemic activity by transgenic expression of a chimeric antigen receptor (CAR) targeting CD19 expressed on B-ALL. PB-derived CAR+ CTLs produced interferon-γ (IFNγ) in response to cytomegalovirus-pp65, adenovirus-hexon, and Epstein-Barr virus pepmixes (from 205 ± 104 to 1034 ± 304 spot-forming cells [SFCs]/105 T cells) and lysed primary B-ALL blasts in 51Cr-release assays (mean, 66% ± 5% specific lysis; effector-target [E/T] ratio, 40:1) and the CD19+ Raji cell line (mean, 78% ± 17%) in contrast to nontransduced controls (8% ± 8% and 3% ± 2%). CB-derived CAR+ CTLs showed similar antiviral and antitumor function and both PB and CB CAR+ CTLs completely eliminated B-ALL blasts over 5 days of coculture. This approach may prove beneficial for patients with high-risk B-ALL who have recently received an HSC or CB transplant and are at risk of infection and relapse.
COPD prevalence and its association with occupational exposures in a general population
Authors: Melville A.M. , Pless-Mulloli T. , Afolabi O.A. , Stenton S.C. 
Published: January 2010

The aim of this study was to ascertain the population prevalence of chronic obstructive pulmonary disease (COPD) in an area with past heavy industry and to establish the relative contributions of occupational and other risk factors.We investigated respiratory symptoms and the prevalence of spirometrically-defined COPD in a population-based study in North-East England (UK) between 2002 and 2004. Questionnaires were posted to 6,000 males and 6,000 females, 45–69 yrs of age, who were randomly selected from a primary care database (response rate 64%, n = 7,566). Spirometric measurements were performed on 845 randomly selected responders. We defined COPD by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II criteria.The prevalence of respiratory symptoms was 55%. Symptoms were strongly associated with smoking, occupational exposures and hay fever. COPD was present in 10% of subjects. Its presence was significantly associated with occupational exposures, smoking and hay fever.COPD is common in North-East England. Respiratory effects of occupational exposures can be detected within the general population: there were clear associations between occupational exposures and respiratory symptoms. The association with COPD was more marked in females.
Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD
Authors: Vogiatzis I. , Simoes D.C.M. , Stratakos G. , Kourepini E. , Terzis G. , Manta P. , Athanasopoulos D. , Roussos C. , Wagner P.D. , Zakynthinos S. 
Published: January 2010

It is known that non-cachectic patients with chronic obstructive pulmonary disease (COPD) respond well to pulmonary rehabilitation, but whether cachectic COPD patients are capable of adaptive responses is both important and unknown.10 cachectic and 19 non-cachectic COPD patients undertook high-intensity cycling training, at the same relative intensity, for 45 min·day−1, 3 days·week−1for 10 weeks. Before and after rehabilitation vastus lateralis muscle biopsies were analysed morphologically and for the expression of muscle remodelling factors (insulin-like growth factor (IGF)-I, myogenic differentiation factor D (MyoD), tumour necrosis factor (TNF)-α, nuclear factor (NF)-κB and myostatin) and key components of ubiquitin-mediated proteolytic systems (muscle ring finger protein (MURF)-1 and Atrogin-1).Rehabilitation improved peak work-rate and the 6-min walk distance similarly in non-cachectic (18±3% and 42±13 m, respectively) and cachectic (16±2% and 53±16 m, respectively) patients, but quality of life only improved in non-cachectic COPD. Mean muscle fibre cross-sectional area increased in both groups, but significantly less in cachectic (7±2%) than in non-cachectic (11±2%) patients. Both groups equally decreased the proportion of type IIb fibres and increased muscle capillary/fibre ratio. IGF-I mRNA expression increased in both groups, but IGF-I protein levels increased more in non-cachectic COPD. MyoD was upregulated, whereas myostatin was downregulated at the mRNA and protein level only in non-cachectic patients. Whilst rehabilitation had no effect on TNF-α expression, it decreased the activation of the transcription factor NF-κB in both groups by the same amount. Atrogin-1 and MURF-1 expression were increased in cachectic COPD, but it was decreased in non-cachectic patients.Cachectic COPD patients partially retain the capacity for peripheral muscle remodelling in response to rehabilitation and are able to increase exercise capacity as much as those without cachexia, even if they exhibit both quantitative and qualitative differences in the type of muscle fibre remodelling in response to exercise training.
Identification of a novel water-soluble activator of wild-type and F508del CFTR: GPact-11a
Authors: Bertrand J. , Boucherle B. , Billet A. , Melin-Heschel P. , Dannhoffer L. , Vandebrouck C. , Jayle C. , Routaboul C. , Molina M-C. , Décout J-L. , Becq F. , Norez C. 
Published: January 2010

One of the major therapeutic strategy in cystic fibrosis aims at developing modulators of cystic fibrosis transmembrane conductance regulator (CFTR) channels. We recently discovered methylglyoxal α-aminoazaheterocycle adducts, as a new family of CFTR inhibitors. In a structure–activity relationship study, we have now identified GPact-11a, a compound able not to inhibit but to activate CFTR.Here, we present the effect of GPact-11a on CFTR activity usingin vitro(iodide efflux, fluorescence imaging and patch-clamp recordings),ex vivo(short-circuit current measurements) andin vivo(salivary secretion) experiments.We report that GPact-11a: 1) is an activator of CFTR in several airway epithelial cell lines; 2) activates rescued F508del-CFTR in nasal, tracheal, bronchial, pancreatic cell lines and in human CF ciliated epithelial cells, freshly dissociated from lung samples; 3) stimulatesex vivothe colonic chloride secretion and increasesin vivothe salivary secretion incftr+/+but notcftr−/−mice; and 4) is selective for CFTR because its effect is inhibited by CFTRinh-172, GlyH-101, glibenclamide and GPinh-5a.To conclude, this work identifies a selective activator of wild-type and rescued F508del-CFTR. This nontoxic and water-soluble agent represents a good candidate, alone or in combination with a F508del-CFTR corrector, for the development of a CFTR modulator in cystic fibrosis.
Measuring asthma control: a comparison of three classification systems
Authors: O’Byrne P.M. , Reddel H.K. , Eriksson G. , Östlund O. , Peterson S. , Sears M.R. , Jenkins C. , Humbert M. , Buhl R. , Harrison T.W. , Quirce S. , Bateman E.D. 
Published: January 2010

There are various ways to classify asthma control; however, no classification is universally accepted. This retrospective analysis compared asthma control as assessed by the Asthma Control Questionnaire (5-item version; ACQ-5), Global Initiative for Asthma (GINA) or Gaining Optimal Asthma Control (GOAL) study criteria.Pooled data at the final study week (n = 8,188) from three budesonide/formoterol maintenance and reliever therapy studies which measured ACQ-5 were stratified according to GINA or GOAL criteria and ACQ-5 score distribution. The percentages of patients with a controlled/partly controlled week (GINA), totally/well-controlled week (GOAL) and range of ACQ-5 cut-off points were compared.Patients with GINA controlled, partly controlled and uncontrolled asthma had mean ACQ-5 scores of 0.43, 0.75 and 1.62, respectively. Patients with GOAL totally controlled, well-controlled and uncontrolled asthma had ACQ-5 scores of 0.39, 0.78 and 1.63. The kappa measure of agreement was 0.80 for GINA and GOAL criteria, and 0.63 for GINA controlled/partly controlled and ACQ-5 <1.00. ACQ-5 detected clinically important improvements in 49% of patients who, according to GINA criteria, remained uncontrolled at the end of the study.Asthma control measured by GINA or GOAL criteria provides similar results. GINA Controlled/Partly Controlled and GOAL Totally Controlled/Well-Controlled correspond to ACQ-5 <1.00. The ACQ-5 is more responsive to change in a clinical trial setting than a categorical scale.
MEK modulates force-fluctuation-induced relengthening of canine tracheal smooth muscle
Authors: Dowell M.L. , Lavoie T.L. , Lakser O.J. , Dulin N.O. , Fredberg J.J. , Gerthoffer W.T. , Seow C.Y. , Mitchell R.W. , Solway J. 
Published: January 2010

Tidal breathing, and especially deep breathing, is known to antagonise bronchoconstriction caused by airway smooth muscle (ASM) contraction; however, this bronchoprotective effect of breathing is impaired in asthma. Force fluctuations applied to contracted ASMin vitrocause it to relengthen, force-fluctuation-induced relengthening (FFIR). Given that breathing generates similar force fluctuations in ASM, FFIR represents a likely mechanism by which breathing antagonises bronchoconstriction. Thus it is of considerable interest to understand what modulates FFIR, and how ASM might be manipulated to exploit this phenomenon. It was demonstrated previously that p38 mitogen-activated protein kinase (MAPK) signalling regulates FFIR in ASM strips. Here, it was hypothesised that the MAPK kinase (MEK) signalling pathway also modulates FFIR.In order to test this hypothesis, changes in FFIR were measured in ASM treated with the MEK inhibitor, U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene).Increasing concentrations of U0126 caused greater FFIR. U0126 reduced extracellular signal-regulated kinase 1/2 phosphorylation without affecting isotonic shortening or 20-kDa myosin light chain and p38 MAPK phosphorylation. However, increasing concentrations of U0126 progressively blunted phosphorylation of high-molecular-weight caldesmon (h-caldesmon), a downstream target of MEK. Thus changes in FFIR exhibited significant negative correlation with h-caldesmon phosphorylation.The present data demonstrate that FFIR is regulated through MEK signalling, and suggest that the role of MEK is mediated, in part, through caldesmon.
Th2-associated immunity to bacteria in teenagers and susceptibility to asthma
Authors: Hollams E.M. , Hales B.J. , Bachert C. , Huvenne W. , Parsons F. , de Klerk N.H. , Serralha M. , Holt B.J. , Ahlstedt S. , Thomas W.R. , Sly P.D. , Holt P.G. 
Published: January 2010

Bacterial colonisation of the airways is associated with increased risk of childhood asthma. Immunoglobulin (Ig)E against bacterial antigens has been reported in some asthmatics, suggesting a role for bacterial-specific type-2 immunity in disease pathogenesis. We aimed to investigate relationships between bacterial-specific IgE amongst teenagers and asthma susceptibility.We measured titres of IgE againstHaemophilus influenzae,Streptococcus pneumoniaeandStaphylococcus aureusin 1,380 teenagers, and related these to asthma symptomatology and immunophenotypes.IgE titres againstS. aureus-derived enterotoxins were highest amongst atopics and were associated with asthma risk. Surprisingly, IgE titres againstH. influenzaeandS. pneumoniaesurface antigens were higher, not stratified by atopy and independently associated with decreased asthma risk.The positive association between type-2 immunity toS. aureusand asthma phenotypes probably reflects IgE-mediated effector cell activationviaenterotoxin super antigens which are secreted in soluble form. The contrasting benign nature of type-2 immunity toH. influenzaeandS. pneumoniaeantigens may reflect their lower availability in soluble forms that can crosslink IgE receptors. We theorise that instead they may be processed by antigen presenting cells and presented to type-2 memory cells leading to mucosal secretion of interleukin (IL)-4/IL-13, a mechanism widely recognised in other tissues to attenuate T-helper-1 associated bacterial-induced inflammation.