bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bruton's tyrosine kinase prevents activation of the anti‐apoptotic transcription factor STAT3 and promotes apoptosis in neoplastic B‐cells and B‐cell precursors exposed to oxidative stress
Authors: Uckun Fatih , Ozer Zahide , Vassilev Alexei 
Published: January 2007

SummaryBruton's tyrosine kinase (BTK) was previously demonstrated to be a mediator of oxidative stress‐induced apoptosis in irradiated neoplastic B‐cells and B‐cell precursors. Defective BTK expression in leukaemic B‐cell precursors from infants with t(4;11) acute lymphoblastic leukaemia has been associated with radiation resistance. The present study examined whether BTK mediates apoptosis during oxidative stress by interfering with the anti‐apoptotic function of signal transducer and activator of transcription 3 (STAT3). BTK physically associated with and tyrosine phosphorylated STAT3; this association was promoted by pervanadate (PV)‐induced oxidative stress. The BTK/STAT3 interaction appeared to prevent STAT3 response to oxidative stress, because PV‐induced STAT3 activation was markedly enhanced in DT40 chicken lymphoma B‐cells that were rendered BTK‐deficient by targeted disruption of the btk gene as well as in BTK‐deficient RAMOS‐1 human lymphoma B‐cells. These BTK‐deficient cells were highly resistant to oxidative stress‐induced apoptosis triggered by PV treatment. Reconstitution of BTK‐deficient DT40 cells with wild‐type human BTK gene eliminated the amplification of the STAT3 response and restored the PV‐induced apoptotic signal. Similarly, while the BTK‐positive NALM‐6 human leukaemic B‐cell precursor cell line showed no STAT3 activation after PV treatment and was exquisitely sensitive to PV‐induced apoptosis, PV failed to induce apoptosis in BTK‐deficient RAMOS‐1 human lymphoma B‐cells that showed a robust STAT3 response. These results provide unprecedented biochemical and genetic evidence for a unique mode of cross‐talk that occurs between BTK and STAT3 pathways during oxidative stress, whereby BTK may trigger apoptosis via negative regulation of the anti‐apoptotic STAT3 activity.
Effects of testosterone and nandrolone on cardiac function: a randomized, placebo‐controlled study
Authors: Chung T. , Kelleher S. , Liu P. Y. , Conway A. J. , Kritharides L. , Handelsman D. J. 
Published: January 2007

SummaryBackground  Androgens have striking effects on skeletal muscle, but the effects on human cardiac muscle function are not well defined, neither has the role of metabolic activation (aromatization, 5α reduction) of testosterone on cardiac muscle been directly studied.Objective  To assess the effects of testosterone and nandrolone, a non‐amplifiable and non‐aromatizable pure androgen, on cardiac muscle function in healthy young men.Design  Double‐blind, randomized, placebo‐controlled, three‐arm parallel group clinical trial.Setting  Ambulatory care research centre.Participants  Healthy young men randomized into three groups of 10 men.Intervention  Weekly intramuscular injections of testosterone (200 mg mixed esters), nandrolone (200 mg nandrolone decanoate) or matching (2 ml arachis oil vehicle) placebo for 4 weeks.Main outcome measures  Comprehensive measures of cardiac muscle function involving transthoracic cardiac echocardiography measuring myocardial tissue velocity, peak systolic strain and strain rates, and bioimpedance measurement of cardiac output and systematic vascular resistance.Results  Left ventricular (LV) function (LV ejection fraction, LV modified TEI index), right ventricular (RV) function (ejection area, tricuspid annular systolic planar motion, RV modified TEI index) as well as cardiac afterload (mean arterial pressure, systemic vascular resistance) and overall cardiac contractility (stroke volume, cardiac output) were within age‐ and gender‐specific reference ranges and were not significantly (P < 0·05) altered by either androgen or placebo over 4 weeks of treatment. Minor changes remaining within normal range were observed solely within the testosterone group for: increased LV end‐systolic diameter (30 ± 7 vs. 33 ± 5 mm, P = 0·04) and RV end‐systolic area (12·8 ± 1·3 vs. 14·6 ± 3·3 cm2, P = 0·04), reduced LV diastolic septal velocity (Em, 9·5 ± 2·6 vs. 8·7 ± 2·0 cm/s, P = 0·006), increased LV filling pressure (E/Em ratio, 7·1 ± 1·6 vs. 8·3 ± 1·8, P = 0·02) and shortened PR interval on the electrocardiogram (167 ± 13 vs. 154 ± 12, P = 0·03).Conclusion  Four weeks of treatment with testosterone or nandrolone had no benefical or adverse effects compared with placebo on cardiac function in healthy young men.
Primary testicular failure in Klinefelter's syndrome: the use of bivariate luteinizing hormone‐testosterone reference charts
Authors: Aksglaede Lise , Andersson Anna‐Maria , Jørgensen Niels , Jensen Tina Kold , Carlsen Elisabeth , McLachlan Robert I. , Skakkebæk Niels E. , Petersen Jørgen Holm , Juul Anders 
Published: January 2007

SummaryBackground  The diagnosis of androgen deficiency is based on clinical features and confirmatory low serum testosterone levels. In early primary testicular failure, a rise in serum LH levels suggests inadequate androgen action for the individual's physiological requirements despite a serum testosterone level within the normal range. The combined evaluation of serum LH and testosterone levels in the evaluation of testicular failure has not been widely advocated.Patients  Seven hundred and six healthy males and 39 patients with known primary hypogonadism due to Klinefelter's syndrome and SRY‐positive 46,XX karyotypes were included in the study.Design  Testosterone, oestradiol and LH serum concentrations were measured in all individuals. Based on the 706 healthy males two‐dimensional bivariate LH‐testosterone reference charts were constructed.Results  Despite a median serum total and free testosterone and oestradiol levels being reduced (P < 0·001) and LH levels elevated (P < 0·001) in Klinefelter's syndrome and 46,XX‐males, many subjects (69%) had total testosterone within the reference range. However, using the bivariate charts all subjects lay outside the 97·5 percentile.Conclusion  Bivariate LH and testosterone charts are useful in the evaluation of men with known primary testicular failure due to sex chromosomal aneuploidy in whom evaluation based on testosterone measurement in isolation underestimates the prevalence of hypogonadism. It is, however, important to emphasize that isolated use of the bivariate evaluation should not form the basis for androgen substitution therapy. Further studies are needed in order to evaluate the use of bivariate LH and testosterone charts in the assessment of any younger man with possible primary testicular failure.
Serum levels of adiponectin and IGFBP‐1 in short children born small for gestational age
Authors: Kamoda Tomohiro , Nozue Hiroki , Matsui Akira 
Published: January 2007

SummaryObjective  The aim of this study was to quantify serum adiponectin concentrations in short children born small for gestational age (SGA) compared with those in children born appropriate for gestational age (AGA), and to assess the relationship between the serum levels of adiponectin and insulin‐like growth factor binding protein‐1 (IGFBP‐1) known as a predictor of the development of type 2 diabetes mellitus and cardiovascular disease.Subjects and methods  Sixteen prepubertal short children born SGA and 20 short children born AGA, matched for age, body mass index, height, pubertal status, gestational age, bone age and midparental height, were included in the study. The serum levels of adiponectin, IGFBP‐1, insulin and insulin‐like growth factor‐I (IGF‐I) were measured in the fasting state.Results  The levels of serum adiponectin were significantly lower in the SGA than in AGA children (10·5 ± 4·2 vs. 13·9 ± 5·1 µg/ml, P < 0·05). The levels of serum IGFBP‐1, insulin and IGF‐I were all similar in both groups. Overall, there was a significant positive correlation between adiponectin and IGFBP‐1 (r = 0·40, P < 0·05).Conclusions  Our results suggest that hypoadiponectinaemia in short SGA children without catch‐up growth may reflect insulin resistance and imply a higher risk of developing type 2 diabetes mellitus. Additionally, adiponectin may be a more sensitive indicator for latent insulin resistance than IGFBP‐1 in short SGA children.
Growth hormone distribution kinetics are markedly reduced in adults with growth hormone deficiency
Authors: Catalina Pablo F. , Páramo Concepción , Andrade Maria Amalia , Mallo Federico 
Published: January 2007

SummaryObjective  Growth hormone (GH) circulating levels are highly dependent not only on GH secretion rate from the pituitary, but also on the hormone distribution in the compartments of the body and elimination phenomena. In adult GH‐deficient patients these factors become critical nowadays, especially when recombinant human GH (rhGH) is available for replacement therapy. In the present study, we assess the influence of both distribution and elimination phenomena on GH pharmacokinetics in adult GH‐deficient patients.Methods  We used a four‐step methodology following a compartmental approach after an intravenous bolus of recombinant GH in adult GH‐deficient patients.Results  We found that GH kinetics are clearly explained by a bi‐exponential, two‐compartmental model in GH‐deficient patients, similarly than in normal or diabetic subjects, as previously shown. We have also observed a marked delay in the whole GH elimination process in GH‐deficient patients compared to normal adult subjects, as revealed by metabolic clearance ratio (MCR), elimination constant from central compartment (k10), and mean resident time in the body (MRT). Interestingly, such a delay appear to be caused by deep changes in the distribution phase (Mtt1– mean transit time‐1; T1/2α– GH half‐life at distribution phase), while the elimination phenomenon remains unaltered.Conclusion  Our results emphasize the relevance of distribution phenomena in GH pharmacokinetics, and indicates that studies avoiding data from the GH distribution phase, such as those carried out in steady‐state conditions, or those using noncompartmental models, could easily miss relevant information. Our data should be taken into consideration when establishing the appropriate dosage for GH replacement treatments in GH‐deficient patients, and calculations should include GH distribution kinetics.
Temperature and soil moisture effects on dissolved organic matter release from a moorland Podzol O horizon under field and controlled laboratory conditions
Authors: Stutter M. I. , Lumsdon D. G. , Cooper R. J. 
Published: January 2007

SummaryOrganic upland soils store large amounts of humified organic matter. The mechanisms controlling the leaching of this C pool are not completely understood. To examine the effects of temperature and microbial cycling on C leaching, we incubated five unvegetated soil cores from a Podzol O horizon (from NE Scotland), over a simulated natural temperature cycle for 1 year, whilst maintaining a constant soil moisture content. Soil cores were leached with artificial rain (177 mm each, monthly) and the leachates analysed for dissolved organic carbon (DOC) and their specific C‐normalized UV absorbance determined (SUVA, 285 nm). Monthly values of respiration of the incubated soils were determined as CO2 efflux. To examine the effects of vegetation C inputs and soil moisture, in addition to temperature, we sampled O horizon pore waters in situ and collected five additional field soil cores every month. The field cores were leached under controlled laboratory conditions. Hysteresis in the monthly amount of DOC leached from field cores resulted in greater DOC on the rising, than falling temperature phases. This hysteresis suggested that photosynthetic C stimulated greater DOC losses in early summer, whereas limitations in the availability of soil moisture in late summer suppressed microbial decomposition and DOC loss. Greater DOC concentrations of in‐situ pore waters than for any core leachates were attributed to the effects of soil drying and physico‐chemical processes in the field. Variation in the respiration rates for the incubated soils was related to temperature, and respiration provided a greater pathway of C loss (44 g C m−2 year−1) than DOC (7.2 g C m−2 year−1). Changes in SUVA over spring and summer observed in all experimental systems were related to the period of increased temperature. During this time, DOC became less aromatic, which suggests that lower molecular weight labile compounds were not completely mineralized. The ultimate DOC source appears to be the incomplete microbial decomposition of recalcitrant humified C. In warmer periods, any labile C that is not respired is leached, but in autumn either labile C production ceases, or it is sequestered in soil biomass.
Iron speciation in soils and soil aggregates by synchrotron‐based X‐ray microspectroscopy (XANES,μ‐XANES)
Authors: Prietzel J. , Thieme J. , Eusterhues K. , Eichert D. 
Published: January 2007

SummaryIron speciation in soils is still poorly understood. We have investigated inorganic and organic standard substances, diluted mixtures of common Fe minerals in soils (pyrite, ferrihydrite, goethite), soils in a forested watershed which constitute a toposequence with a hydrological gradient (Dystric Cambisol, Dystric Planosol, Rheic Histosol), and microsites of a dissected soil aggregate by X‐ray Absorption Near Edge Spectroscopy (XANES) at the iron K‐edge (7112 eV) to identify different Fe(II) and Fe(III) components. We calculated the pre‐edge peak centroid energy of all spectra and quantified the contribution of different organic and inorganic Fe‐bearing compounds by Linear Combination Fitting (LCF) conducted on the entire spectrum (E = 7085–7240 eV) and on the pre‐edge peak. Fe‐XANES conducted on organic and inorganic standards and on synthetic mixtures of pyrite, ferrihydrite and goethite showed that by calculating the pre‐edge peak centroid energy, the Fe(II)/Fe(III) ratio of different Fe‐bearing minerals (Fe sulphides, Fe oxyhydroxides) in mineral mixtures and soils can be quantified with reasonable accuracy. A more accurate quantification of the Fe(II)/Fe(III) ratio was possible with LCF conducted on the entire XANES spectrum. For the soil toposequence, an increased groundwater influence from the Cambisol to the Histosol was reflected in a larger contribution of Fe(II) compounds (Fe(II) silicate, Fe monosulphide, pyrite) and a smaller contribution of Fe(III) oxyhydroxides (ferrihydrite, goethite) to total iron both in the topsoil and the subsoil. In the organic topsoils, organically bonded Fe (33–45% of total Fe) was 100% Fe(III). For different microsites in the dissected aggregate, spatial resolution ofμ‐XANES revealed different proportions of Fe(II) and Fe(III) compounds. Fe K‐edge XANES andμ‐XANES allows an approximate quantification of Fe(II) and Fe(III) and different Fe compounds in soils and (sub)micron regions of soil sections, such as mottles, concretions, and rhizosphere regions, thus opening new perspectives in soil research.
Allocation and residence time of photosynthetic products in a boreal forest using a low‐level 14C pulse‐chase labeling technique
Authors: CARBONE MARIAH S. , CZIMCZIK CLAUDIA I. , McDUFFEE KELSEY E. , TRUMBORE SUSAN E. 
Published: January 2007

AbstractMuch of our understanding about how carbon (C) is allocated in plants comes from radiocarbon (14C) pulse‐chase labeling experiments. However, the large amounts of 14C required for decay‐counting mean that these studies have been restricted for the most part to mesocosm or controlled laboratory experiments. Using the enhanced sensitivity for 14C detection available with accelerator mass spectrometry (AMS), we tested the utility of a low‐level 14C pulse‐chase labeling technique for quantifying C allocation patterns and the contributions of different plant components to total ecosystem respiration in a black spruce forest stand in central Manitoba, Canada. All aspects of the field experiment used 14C at levels well below regulated health standards, without significantly altering atmospheric CO2 concentrations. Over 30 days following the label application in late summer (August and September), we monitored the temporal and spatial allocation patterns of labeled photosynthetic products by measuring the amount and 14C content of CO2 respired from different ecosystem components. The mean residence times (MRT) for labeled photosynthetic products to be respired in the understory (feather mosses), canopy (black spruce), and rhizosphere (black spruce roots and associated microbes) were <1, 6, and 15 days, respectively. Respiration from the canopy and understory showed significantly greater influence of labeled photosynthates than excised root and intact rhizosphere respiration. After 30 days,∼65% of the label assimilated had been respired by the canopy,∼20% by the rhizosphere, and∼9% by the understory, with∼6% unaccounted for and perhaps remaining in tissues. Maximum 14C values in root and rhizosphere respiration were reached 4 days after label application. The label was still detectable in root, rhizosphere and canopy respiration after 30 days; these levels of remaining label would not have been detectible had a 13C label been applied. Our results support previous studies indicating that a substantial portion of the C fueling rhizosphere respiration in the growing season may be derived from stored C pools rather than recent photosynthetic products.
Elevated CO2 increases microbial carbon substrate use and nitrogen cycling in Mojave Desert soils
Authors: JIN V. L. , EVANS R. D. 
Published: January 2007

AbstractIdentifying soil microbial responses to anthropogenically driven environmental changes is critically important as concerns intensify over the potential degradation of ecosystem function. We assessed the effects of elevated atmospheric CO2 on microbial carbon (C) and nitrogen (N) cycling in Mojave Desert soils using extracellular enzyme activities (EEAs), community‐level physiological profiles (CLPPs), and gross N transformation rates. Soils were collected from unvegetated interspaces between plants and under the dominant shrub (Larrea tridentata) during the 2004–2005 growing season, an above‐average rainfall year. Because most measured variables responded strongly to soil water availability, all significant effects of soil water content were used as covariates to remove potential confounding effects of water availability on microbial responses to experimental treatment effects of cover type, CO2, and sampling date. Microbial C and N activities were lower in interspace soils compared with soils under Larrea, and responses to date and CO2 treatments were cover specific. Over the growing season, EEAs involved in cellulose (cellobiohydrolase) and orthophosphate (alkaline phosphatase) degradation decreased under ambient CO2, but increased under elevated CO2. Microbial C use and substrate use diversity in CLPPs decreased over time, and elevated CO2 positively affected both. Elevated CO2 also altered microbial C use patterns, suggesting changes in the quantity and/or quality of soil C inputs. In contrast, microbial biomass N was higher in interspace soils than soils under Larrea, and was lower in soils exposed to elevated CO2. Gross rates of NH4+ transformations increased over the growing season, and late‐season NH4+ fluxes were negatively affected by elevated CO2. Gross NO3− fluxes decreased over time, with early season interspace soils positively affected by elevated CO2. General increases in microbial activities under elevated CO2 are likely attributable to greater microbial biomass in interspace soils, and to increased microbial turnover rates and/or metabolic levels rather than pool size in soils under Larrea. Because soil water content and plant cover type dominates microbial C and N responses to CO2, the ability of desert landscapes to mitigate or intensify the impacts of global change will ultimately depend on how changes in precipitation and increasing atmospheric CO2 shift the spatial distribution of Mojave Desert plant communities.
Development and characterization of novel photosensitizer :  scFv conjugates for use in photodynamic therapy of cancer
Authors: Staneloudi Chrysovalanto , Smith Karen A. , Hudson Robert , Malatesti Nela , Savoie Huguette , Boyle Ross W. , Greenman John 
Published: January 2007

SummaryPhotodynamic therapy (PDT) is becoming an evermore useful tool in oncology but is frequently limited by side‐effects caused by a lack of targeting of the photosensitizer. This problem can often be circumvented by the conjugation of photosensitizers to tumour‐specific monoclonal antibodies. An alternative is the use of single chain (sc) Fv fragments which, whilst retaining the same binding specificity, are more efficient at penetrating tumour masses because of their smaller size; and are more effectively cleared from the circulation because of the lack of an Fc domain. Here we describe the conjugation of two isothiocyanato porphyrins to colorectal tumour‐specific scFv, derived from an antibody phage display library. The conjugation procedure was successfully optimized and the resulting immunoconjugates showed no loss of cell binding. In vitro assays against colorectal cell lines showed these conjugates had a selective photocytotoxic effect on cells. Annexin V and propidium iodide staining of treated cells confirmed cell death was mediated principally via an apoptotic pathway. This work suggests that scFv : porphyrin conjugates prepared using isothiocyanato porphyrins show promise for use as targeted PDT agents.
Evolution of sex chromosomes: dosage compensation of the Lcp1–4 gene cluster on the evolving neo‐X chromosome in Drosophila miranda
Authors: Steinemann S. , Steinemann M. 
Published: January 2007

AbstractIn Drosophila miranda the small multigene family of the larval cuticle protein (Lcp1–4) genes resides on the evolving neo‐X and neo‐Y sex chromosome pair while in the sibling species Drosophila pseudoobscura and Drosophila persimilis the gene cluster is inherited autosomally. The neo‐Y chromosomal Lcp1, Lcp2 and Lcp4 genes are, as previously shown by us, not expressed and only Lcp3 is expressed at a strongly reduced level. As a first step in understanding the evolutionary mechanism(s) transforming an autosome into a dosage compensated X we analysed the expression behaviour and promoter structure of the Lcp1–4 genes on the neo‐X. The normalized relative expression levels reveal that all four neo‐X chromosomal Lcp genes in D. miranda males, including Lcp3, are already dosage compensated.
An α‐amylase (At4g25000) in Arabidopsis leaves is secreted and induced by biotic and abiotic stress
Authors: DOYLE ELIZABETH A. , LANE ASHLEIGH M. , SIDES JAMES M. , MUDGETT MARY BETH , MONROE JONATHAN D. 
Published: January 2007

ABSTRACTLeaves are reported to contain a secreted α‐amylase that accumulates during senescence or after biotic or abiotic stress; however, a gene encoding this enzyme has not been described. Because a secreted amylase is isolated from plastidic starch, the function of this enzyme is difficult to predict, but circumstantial evidence suggests that it may degrade starch after cell death. The Arabidopsis thaliana genome contains three α‐amylase genes, one of which, AMY1 (At4g25000), has a putative signal sequence suggesting that the protein may be secreted. Two independent T‐DNA insertion mutants in AMY1 lacked an amylase band on starch zymograms, which was previously named ‘A1’. Washed leaf protoplasts contained reduced A1 activity suggesting that the enzyme is secreted. Native AMY1, fused to a weakly fluorescent form of GFP, was sensitive to proteinase K infiltrated into leaf apoplastic spaces, while a cytosolic form of GFP was unaffected until cell breakage, confirming that the AMY1 protein is secreted. Amylase A1 was transcriptionally induced in senescing leaves and in leaves exposed to heat stress, treated with abscisic acid or infected with Pseudomonas syringae pv. tomato expressing avrRpm1. The A1 amylase was also extremely heat resistant and its expression was up‐regulated in cpr5‐2, an activated defence response mutant.