bluuebunny/crossref_metadata_2025_split huggingface dataset:
B lymphocyte‐induced maturation protein‐1 (Blimp‐1) is sufficient to trigger an unfolded protein response and XBP‐1 processing in B cells
Authors: Vallabhapurapu Duttu S. , Schimpl Anneliese , Berberich Ingolf 
Published: January 2006

AbstractTerminal differentiation of B cells into antibody secreting plasma cells is an essential step for eliciting a successful humoral immune response. The two transcription factors B lymphocyte‐induced maturation protein‐1 (Blimp‐1) and X‐box‐binding protein‐1 (XBP‐1) are indispensable for this process. Hereby, XBP‐1 activation depends on Blimp‐1. However, it is not known if Blimp‐1 alone, in the absence of differentiation signals, can induce XBP‐1 processing. Here we show that ectopic expression of Blimp‐1 is sufficient to induce an unfolded protein response (UPR), as evidenced by the generation of the processed form of XBP‐1 and upregulation of the classical UPR target BIP, in both the B cell lymphoma cell line WEHI 231 and in mouse primary splenic B cells. Interestingly, the amino terminal part of Blimp‐1 comprising amino acids 1‐751 was sufficient to induce the above effects while the carboxy terminal part comprising amino acids 465‐856 had no effect. Taken together our results identify Blimp‐1 as the upstream molecule, capable of triggering the UPR in B cells resulting in XBP‐1 processing, which is an important step during plasma cell generation.
Chemical intervention in signalling networks: recent advances and applications
Authors: Tate Edward William 
Published: January 2006

AbstractChemical intervention in biological systems is a field undergoing explosive growth, and a growing number of applications in signal transduction have evolved from the rich variety of small molecule and other chemical tools now available for selective modulation of cellular processes. The key enabling factor for the majority of recent discoveries has been close collaboration between chemists and cell biologists, bringing together expertise in the development and application of novel and biologically‐relevant chemistry and an understanding of where these techniques can be brought to bear for greatest effect. The core technologies of chemical genetics, diversity oriented synthesis, high‐throughput screening and microarray technologies have recently been used in various combinations to shed light on an impressive diversity of areas, including neural lipid and auxin signalling, membrane protein co‐localisation, protein kinase engineering, and imaging signalling‐related processes. While further innovation is required to demonstrate the full potential for selective chemical intervention to complement and to a degree supersede pure genetic approaches, it will continue to stimulate ground‐breaking research, in both chemistry and biology, for many years to come.
Measurement of the mechanical properties of the skin using the suction test
Authors: Khatyr Fouad , Imberdis Claude , Varchon Daniel , Lagarde Jean‐Michel , Josse Gwendal 
Published: January 2006

Introduction: The suction test is commonly used to study the mechanical properties of human skin in vivo. The unevenness of the stress fields complicates obtaining the intrinsic mechanical parameters of the skin in vivo because the values of the local stresses and deformations cannot be calculated directly from the displacements and forces applied by the test apparatus. In general, users only take into account the negative pressure applied and the elevation of the dome of skin drawn up in order to deduce the properties of the skin. This method has the major disadvantage of being dependent on the experimental conditions used: in particular, the size of the suction cup and the negative pressure applied. Here, we propose a full mechanical study of the test to provide rigorous results. We compare the frequently used geometric method (making the thin plate hypothesis), Timoshenko's method (which can take greater plate thicknesses into account) and finally various results obtained by the finite elements (FE) technique.Methods: The suction test was modelled by FE with large displacements and large deformations both for orthotropic and isotropic plates. The results obtained in the elastic domain for various values of Young's modulus and of applied negative pressure were used as references and were compared with methods using analytical relationships.Results: The geometric method generally used in the interpretation of suction tests gives results, which in certain configurations, are very different from those obtained by FE. The method of Timoshenko is suited to thick plates ‘in contact’ or embedded round the edge, the elevation of the dome and the tension and flexion stresss are analytically accessible through relationships involving four constants that are dependent on the limit conditions. Comparison with the FE results enabled the optimisation of the coefficients to adapt the relationships to the particular conditions of the suction trials.Conclusion: We showed the limits of the geometrical method and proposed a solution, which while remaining simple to use, gives results that are closer to reality both for the calculation of the modulus and for the determination of the state of the stresses obtained.
Digital camera images obtained using a light‐emitting diode illuminator and their dermatological applications
Authors: Ahn Hyo Hyun , Kim Soo Nam , Kye Young Chul 
Published: January 2006

Background/purpose: Although digital cameras have powerful macrocapabilities, flash macrophotographs are often unsatisfactory. The aim of this study was to develop a light‐emitting diode (LED) illuminator for macro digital photography that allows colorimetric investigations of the skin.Methods: We devised an LED illuminator suitable for acquiring super‐macro digital images of the skin. Reference CIELAB color chart values were compared statistically with computed values from digital images in order to obtain equations for real CIELAB values. Using these, we acquired and analyzed images of various dermatological conditions using an LED illuminator.Results: The images obtained with the devised LED illuminator were more reproducible than flash‐assisted photographs. With proper camera settings, the devised LED illuminator and the color analysis method developed during this study provided digital skin images containing colorimetric information.Conclusion: A digital camera equipped with an LED illuminator is a useful tool for dermatological research and clinical practice.
High‐resolution ultrasound reflex transmission imaging and digital photography: potential tools for the quantitative assessment of pigmented lesions
Authors: Rallan D. , Dickson M. , Bush N. L. , Harland C. C. , Mortimer P. , Bamber J. C. 
Published: January 2006

Background/aims: High‐resolution ultrasound (HRU) is a relatively cheap imaging method that shows small quantitative differences between benign naevi and melanoma. Previous studies using B‐mode display suggest that these arise from their differing attenuating properties. Attenuation characteristics, however, are better evaluated using reflex transmission imaging (RTI). White light clinical (WLC) photography is an even cheaper imaging method that is routinely used for monitoring but less frequently in everyday diagnosis. As features from each method may have an independent origin, two such modalities may be of greater diagnostic value than either method alone. However, although quantitative analysis of digital photographs is being developed to aid tumour diagnosis, in vivo RTI for the evaluation of pigmented skin lesions has not previously been described. This paper presents the feasibility of performing RTI in vivo and evaluates the reliability of the objective features used. The potential of the combination of quantitative RTI and white light (WL) digital photography data for the classification of pigmented lesions was assessed.Methods: Randomly selected patients were recruited via a skin cancer screening clinic. RTI data were acquired from each index lesion with a 20 MHz single‐element scanner. WL images were taken using a high‐resolution (2.8 Mpixels) digital camera. Quantitative features calculated from both images were used to derive a discriminant rule. This equation was then applied to reclassify each case based on its quantitative criteria. The resultant classification was compared with histological diagnosis.Results: Twenty‐four lesions (10 melanoma and 14 naevi) were studied. On RTI, no subjective differences were observed between benign naevi and melanoma. Many lesions were either not visible on RTI or lacked clearly definable borders. Consequently, the WL photographs were used to draw lesion boundaries on RT images for feature calculation. Melanoma were less attenuating than naevi on RTI (P=0.026) and had greater red colour variegation on WL imaging (P=0.016). The combination of quantitative parameters (two from RTI and four from photographs) improved sensitivity for this sample without compromising the specificity of 100% compared with either modality alone. The procedure is highly reproducible (r=0.85 between two operators).Conclusions: Pigmented skin lesions can be quantitatively defined from RTI data acquired in vivo and a significant difference in attenuation is shown. However, accurate registration of the RT image with a corresponding photograph was crucial for this purpose and only possible when corresponding points could be reliably identified on both images. Combination of features from ultrasound and optical images may synergistically improve diagnostic accuracy and a larger study is warranted to investigate this.
When gatekeepers meet the sentinel: the impact of a prior authorization requirement for cefuroxime on the prescribing behaviour of community‐based physicians
Authors: Kahan Natan R. , Chinitz David P. , Waitman Dan‐Andrei , Kahan Ernesto 
Published: January 2006

AimsPrior authorization (PA), the requirement of physicians to obtain pre‐approval as a prerequisite for coverage, may decrease drug utilization via a ‘sentinel effect’, a decrease in utilization caused by external review of prescribing. The purpose of this study was to assess the affect a PA restriction had on the utilization patterns of cefuroxime tablets in a managed care organization (MCO) in Israel.MethodsPhysician prescribing patterns were evaluated by conducting a retrospective drug utilization analysis. Data were derived from the electronic patient records of the MCO studied. All prescriptions for solid state antibiotics for patients diagnosed with an infectious disease written during three parallel 3‐month segments, before, during and after a PA restriction for cefuroxime was enforced, were included. Frequency and proportion of antibiotic prescriptions for cefuroxime tablets, distribution of infectious diseases treated with cefuroxime, and the request rejection rate when PA was required were calculated.ResultsPrescriptions for cefuroxime declined from 5538 prescriptions (8.0% of eligible antibiotic prescriptions, 95% CI 7.8, 8.2) in the initial period to 1036 (1.2%, 95% CI 1.1, 1.3) during the PA period, rising to 3961 (4.3%, 95% CI 4.2, 4.4) in the post‐PA period. Changes in the distribution of diseases treated with cefuroxime during the PA stage tended to regress after revocation to those observed in the pre‐PA period. The rejection rate was found to be 8.5% (95% CI = 6.9, 10.1).ConclusionsThe implementation of a prior authorization requirement for cefuroxime tablets markedly reduced the use of this drug, probably due to a ‘sentinel effect’.
Comparison of ecosystem water‐use efficiency among Douglas‐fir forest, aspen forest and grassland using eddy covariance and carbon isotope techniques
Authors: PONTON STÉPHANE , FLANAGAN LAWRENCE B. , ALSTAD KARRIN P. , JOHNSON BRUCE G. , MORGENSTERN KAI , KLJUN NATASCHA , BLACK T. ANDREW , BARR ALAN G. 
Published: January 2006

AbstractComparisons were made among Douglas‐fir forest, aspen (broad leaf deciduous) forest and wheatgrass (C3) grassland for ecosystem‐level water‐use efficiency (WUE). WUE was defined as the ratio of photosynthetic CO2 assimilation rate and evapotranspiration (ET) rate. The ET data measured by eddy covariance were screened so that they overwhelmingly represented transpiration. The three sites used in this comparison spanned a range of vegetation (plant functional) types and environmental conditions within western Canada. When compared in the relative order Douglas‐fir (located on Vancouver Island, BC), aspen (northern Saskatchewan), grassland (southern Alberta), the sites demonstrated a progressive decline in precipitation and a general increase in maximum air temperature and atmospheric saturation deficit (Dmax) during the mid‐summer. The average (±SD) WUE at the grassland site was 2.6±0.7 mmol mol−1, which was much lower than the average values observed for the two other sites (aspen: 5.4±2.3, Douglas‐fir: 8.1±2.4). The differences in WUE among sites were primarily because of variation in ET. The highest maximum ET rates were approximately 5, 3.2 and 2.7 mm day−1 for the grassland, aspen and Douglas‐fir sites, respectively. There was a strong negative correlation between WUE and Dmax for all sites. We also made seasonal measurements of the carbon isotope ratio of ecosystem respired CO2 (δR) in order to test for the expected correlation between shifts in environmental conditions and changes to the ecosystem‐integrated ratio of leaf intercellular to ambient CO2 concentration (ci/ca). There was a consistent increase in δR values in the grassland, aspen forest and Douglas‐fir forest associated with a seasonal reduction in soil moisture. Comparisons were made between WUE measured using eddy covariance with that calculated based on D and δR measurements. There was excellent agreement between WUE values calculated using the two techniques. Our δR measurements indicated that ci/ca values were quite similar among the Douglas‐fir, aspen and grassland sites, despite large variation in environmental conditions among sites. This implied that the shorter‐lived grass species had relatively high ci/ca values for the D of their habitat. By contrast, the longer‐lived Douglas‐fir trees were more conservative in water‐use with lower ci/ca values relative to their habitat D. This illustrates the interaction between biological and environmental characteristics influencing ecosystem‐level WUE. The strong correlation we observed between the two independent measurements of WUE, indicates that the stable isotope composition of respired CO2 is a useful ecosystem‐scale tool to help study constraints to photosynthesis and acclimation of ecosystems to environmental stress.
Carbon respired by terrestrial ecosystems – recent progress and challenges
Authors: TRUMBORE SUSAN 
Published: January 2006

AbstractNet ecosystem production is the residual of two much larger fluxes: photosynthesis and respiration. While photosynthesis is a single process with a well‐established theoretical underpinning, respiration integrates the variety of plant and microbial processes by which CO2 returns from ecosystems to the atmosphere. Limits to current capacity for predicting ecosystem respiration fluxes across biomes or years result from the mismatch between what is usually measured – bulk CO2 fluxes – and what process‐based models can predict – fluxes of CO2 from plant (autotrophic) or microbial (heterotrophic) respiration. Papers in this Thematic Issue and in the recent literature, document advances in methods for separating respiration into autotrophic and heterotrophic components using three approaches: (1) continuous measurements of CO2 fluxes and assimilation of these data into process‐based models; (2) application of isotope measurements, particularly radiocarbon; and (3) manipulation experiments. They highlight the role of allocation of C fixed by plants to respiration, storage, growth or transfer to other organisms as a control of seasonal and interannual variability in soil respiration and the oxidation state of C in the terrestrial biosphere. A second theme is the potential for comparing C isotope signatures in organic matter, CO2 evolved in incubations and microbial biomarkers to elucidate the pathways (respiration, recycling, or transformation) of C during decomposition. Together, these factors determine the continuum of timescales over which C is returned to the atmosphere by respiration and enable testing of theories of plant and microbial respiration that go beyond empirical models and allow predictions of future respiration responses to future change in climate, pollution and land use.
Effects of patch quality and network structure on patch occupancy dynamics of a yellow‐bellied marmot metapopulation
Authors: OZGUL ARPAT , ARMITAGE KENNETH B. , BLUMSTEIN DANIEL T. , VANVUREN DIRK H. , OLI MADAN K. 
Published: January 2006

SummaryThe presence/absence of a species at a particular site is the simplest form of data that can be collected during ecological field studies. We used 13 years (1990–2002) of survey data to parameterize a stochastic patch occupancy model for a metapopulation of the yellow‐bellied marmot in Colorado, and investigated the significance of particular patches and the influence of site quality, network characteristics and regional stochasticity on the metapopulation persistence.Persistence of the yellow‐bellied marmot metapopulation was strongly dependent on the high quality colony sites, and persistence probability was highly sensitive to small changes in the quality of these sites.A relatively small number of colony sites was ultimately responsible for the regional persistence. However, lower quality satellite sites also made a significant contribution to long‐term metapopulation persistence, especially when regional stochasticity was high.The northern network of the marmot metapopulation was more stable compared to the southern network, and the persistence of the southern network depended heavily on the northern network.Although complex models of metapopulation dynamics may provide a more accurate description of metapopulation dynamics, such models are data‐intensive. Our study, one of the very few applications of stochastic patch occupancy models to a mammalian species, suggests that stochastic patch occupancy models can provide important insights into metapopulation dynamics using data that are easy to collect.
Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune implications in critical illness
Authors: MOLINA P. E. 
Published: January 2006

Abstract.Traumatic injury, surgical interventions and sepsis are amongst some of the clinical conditions that result in marked activation of neuroendocrine and opiate responses aimed at restoring haemodynamic and metabolic homeostasis. The central activation of the neuroendocrine and opiate systems, known collectively as the stress response, is elicited by diverse physical stressor conditions, including ischaemia, glucopenia and inflammation. The role of the hypothalamic–pituitary–adrenal axis and sympathetic nervous system in counterregulation of haemodynamic and metabolic alterations has been studied extensively. However, that of the endogenous opiates/opioid system is still unclear. In addition to activation of the opiate receptor through the endogenous release of opioids, pharmacotherapy with opiate receptor agonists is frequently used for sedation and analgesia of injured, septic and critically ill patients. How this affects the haemodynamic, cardiovascular, metabolic and immune responses is poorly understood. The variety of opiate receptor types, their specificity and ubiquitous location both in the central nervous system and in the periphery adds additional complicating factors to the clear understanding of their contribution to the stress response to the various physical perturbations. This review aims at discussing scientific evidence gathered from preclinical studies on the role of endogenous opioids as well as those administered as pharmacological agents on the host cardiovascular, neuroendocrine, metabolic and immune response mechanisms critical for survival from injury in perspective with clinical observations that provide parallel assessment of relevant outcome measures. When possible, the clinical relevance and corresponding scenarios where this evidence can be integrated into our understanding of the clinical implications of opiate effects will be examined. Overall, the scientific basis to enhance clinical judgment and expectations when using opioid sedation and analgesia in the management of the injured, septic or postsurgical patient will be discussed.
Intra‐abdominal abscess in a patient with tumour necrosis factor receptor‐associated periodic syndrome
Authors: STJERNBERG‐SALMELA S. , KIVISAARI A. , PUOLAKKAINEN P. , FÄRKKILÄ M. , KEMPPAINEN E. , RANKI A. , PETTERSSON T. 
Published: January 2006

Abstract.Tumour necrosis factor (TNF) receptor‐associated periodic syndrome (TRAPS) is an autoinflammatory disorder characterized by periodic attacks of fever and inflammation, due to mutations in the gene coding for the TNF type I receptor (TNFRSF1A). A 16‐year‐old patient with the diagnosis of TRAPS was admitted to hospital because of fever and abdominal pain. Initially, the symptoms were interpreted as manifestations of another TRAPS attack, but the patient's condition worsened, despite treatment with corticosteroids and antibiotics. A repeated computer tomography revealed an intra‐abdominal abscess, which necessitated urgent surgical intervention. This case stresses the importance of differential diagnostic vigilance when dealing with patients with rare genetic diseases.
Aspergillus nidulans class V and VI chitin synthases CsmA and CsmB, each with a myosin motor‐like domain, perform compensatory functions that are essential for hyphal tip growth
Authors: Takeshita Norio , Yamashita Shuichi , Ohta Akinori , Horiuchi Hiroyuki 
Published: January 2006

SummaryThe polarized synthesis of cell wall components such as chitin is essential for the hyphal tip growth of filamentous fungi. The actin cytoskeleton is known to play important roles in the determination of hyphal polarity in Aspergillus nidulans. Previously, we suggested that CsmA, a chitin synthase with a myosin motor‐like domain (MMD), was involved in polarized chitin synthesis in a manner dependent on the interaction between the MMD and the actin cytoskeleton. The genome database indicates that A. nidulans possesses another gene encoding another chitin synthase with an MMD. In this study, we characterized this gene, which we designated csmB. The csmB null mutants examined were viable, although they exhibited defective phenotypes, including the formation of balloons and intrahyphal hyphae and the lysis of subapical regions, which were similar to those obtained with csmA null mutants. Moreover, csmA csmB double null mutants were not viable. Mutants in which csmB was deleted and the expression of csmA was under the control of the alcA promoter were viable but severely impaired in terms of hyphal growth under alcA‐repressing conditions. We revealed that CsmB with three copies of a FLAG epitope tag localized at the hyphal tips and forming septa, and that the MMD of CsmB was able to bind to actin filaments in vitro. These results suggest that CsmA and CsmB perform compensatory functions that are essential for hyphal tip growth.