bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transferable and Negotiated Knowledge
Authors: Närhi Kati 
Published: April 2009

• Summary: This article explores the knowledge of community-based social workers in the context of an action research project aimed at exploring the practitioners’ own descriptions of their knowledge and expertise on the theme of spatial marginalization. • Findings: The knowledge of social workers seemed to be based on service users’ experiences and case examples, on value and moral constructions, and it was created from experience, by doing and in action. It was local and contextual, in some sense silent but shared through a discussion process. It was not based on empirically based scientific research understood in the traditional sense; rather, social workers resorted to practical knowledge in its various forms. • Applications: The sharing of individuals’ social work knowledge, both ‘knowing that’ and ‘knowing how’, with other social workers and reflecting together on the knowledge and tradition that social workers carry serves to define, study and promote the transferability of common and shared knowledge.
Women researching their lives: exploring violence and identity in Belfast, the North of Ireland
Authors: Mcintyre Alice 
Published: April 2009

As the newly elected members of the Northern Ireland Assembly work towards implementing mechanisms for protecting and furthering the economic, social, political, cultural, and civic rights of the people of the North of Ireland, many local people are simultaneously developing strategies for addressing the legacy of violence that has characterized life in that region of the world for over 30 years. In this article, I describe how one group of working-class women living in Belfast address their personal and collective experiences with the multiple forms of violence that structure their daily lives. I do so by describing an ongoing feminist participatory action research (PAR) project that provided the women with a culturally relevant lens through which to view the historical and political contexts in which they live and act. Although there were multiple dimensions of the women’s lives that were revealed in the project, in this article I focus specifically on the ‘frozen watchfulness’ that characterizes life on Monument Road - a watchfulness that is born out of years of living in and with chronic and unpredictable violence. First, I provide an overview of the overall project. Second, I provide a glimpse of how violence acts as an organizer in the women’s lives. Lastly, I discuss the importance of opening up spaces for women living in conflicted communities to speak about their lives and develop strategies for generating new contexts for the revitalization of everyday life.
How I treat paroxysmal nocturnal hemoglobinuria
Authors: Brodsky Robert A. 
Published: April 2009

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is a rare clonal blood disorder that manifests with hemolytic anemia, bone marrow failure, and thrombosis. Many of the clinical manifestations of the disease result from complement-mediated intravascular hemolysis. Allogeneic bone marrow transplantation is the only curative therapy for PNH. Eculizumab, a monoclonal antibody that blocks terminal complement activation, is highly effective in reducing hemolysis, improving quality of life, and reducing the risk for thrombosis in PNH patients. Insights into the relevance of detecting PNH cells in PNH and other bone marrow failure disorders are highlighted, and indications for treating PNH patients with bone marrow transplantation and eculizumab are explored.
Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9
Authors: Peng Tie-Li , Chen Jie , Mao Wei , Song Xin , Chen Min-Hu 
Published: April 2009

AbstractBackgroundAbberant aryl hydrocarbon receptor (AhR) expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism.ResultsTo determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV) could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD (10 nmol/L) treatment, MMP-9 mRNA expression and activity were significant increased; This TCDD-induced MMP-9 expression and activity increase could be abolished by c-Jun siRNA transfection.ConclusionAhR pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of MMP-9. Our results provide insight into the mechanism and function of the AhR pathway and its impact on gastric cancer progression.
Requirements for E1A dependent transcription in the yeast Saccharomyces cerevisiae
Authors: Yousef Ahmed F , Brandl Christopher J , Mymryk Joe S 
Published: April 2009

Abstract

Background
The human adenovirus type 5 early region 1A (E1A) gene encodes proteins that are potent regulators of transcription. E1A does not bind DNA directly, but is recruited to target promoters by the interaction with sequence specific DNA binding proteins. In mammalian systems, E1A has been shown to contain two regions that can independently induce transcription when fused to a heterologous DNA binding domain. When expressed in Saccharomyces cerevisiae, each of these regions of E1A also acts as a strong transcriptional activator. This allows yeast to be used as a model system to study mechanisms by which E1A stimulates transcription.

Results
Using 81 mutant yeast strains, we have evaluated the effect of deleting components of the ADA, COMPASS, CSR, INO80, ISW1, NuA3, NuA4, Mediator, PAF, RSC, SAGA, SAS, SLIK, SWI/SNF and SWR1 transcriptional regulatory complexes on E1A dependent transcription. In addition, we examined the role of histone H2B ubiquitylation by Rad6/Bre1 on transcriptional activation.

Conclusion
Our analysis indicates that the two activation domains of E1A function via distinct mechanisms, identify new factors regulating E1A dependent transcription and suggest that yeast can serve as a valid model system for at least some aspects of E1A function.
Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC)
Authors: Tsui Sam-Mui , Lam Wai-Man , Lam Tin-Lun , Chong Hiu-Chi , So Pui-Kin , Kwok Sui-Yi , Arnold Simon , Cheng Paul Ning-Man , Wheatley Denys N , Lo Wai-Hung , Leung Yun-Chung 
Published: April 2009

Abstract

Background
Protein used in medicine, e.g. interferon, are immunogenic and quickly broken down by the body. Pegylation is a recognized way of preserving their integrity and reducing immune reactions, and works well with enzymes used to degrade amino acids, a recent focus of attention in controlling cancer growth. Of the two arginine-degrading enzymes being explored clinically, arginine deiminase is a decidedly foreign mycoplasm-derived enzyme, whereas human arginase 1 is a native liver enzyme. Both have been pegylated, the former with adjuncts of 20 kD, the latter with 5 kD PEG. Pegylation is done by several different methods, not all of which are satisfactory or desirable.

Methods
The preparation of novel polyethylene glycol (PEG) derivatives for modifying proteins is described, but directed specifically at pegylation of recombinant human arginase 1 (rhArg1). rhArg1 expressed in Escherichia coli was purified and coupled in various ways with 5 different PEG molecules to compare their protective properties and the residual enzyme activity, using hepatocellular cell lines both in vitro and in vivo.

Results
Methoxypolyethylene glycol-succinimidyl propionate (mPEG-SPA 5,000) coupled with very high affinity under mild conditions. The resulting pegylated enzyme (rhArg1-peg5,000 mw) had up to 6 PEG chains of 5K length which not only protected it from degradation and any residual immunogenicity, but most importantly let it retain >90% of its native catalytic activity. It remained efficacious in depleting arginine in rats after a single ip injection of 1,500 U of the conjugate as the native enzyme, plasma arginine falling to >0.05 μM from ~170 μM within 20 min and lasting 6 days. The conjugate had almost the same efficacy as unpegylated rhArg1 on 2 cultured human liver cancer (HCC) cell lines. It was considerably more effective than 4 other pegylated conjugates prepared.

Conclusion
Valuable data on the optimization of the pegylation procedure and choice of ligand that best stabilizes the enzyme arginase 1 are presented, a protocol that should equally fit many other enzymes and proteins. It is a long lasting arginine-depleting enzyme in vivo which will greatly improve its use in anti-cancer therapy.
Environmentally persistent free radicals amplify ultrafine particle mediated cellular oxidative stress and cytotoxicity
Authors: Balakrishna Shrilatha , Lomnicki Slawo , McAvey Kevin M , Cole Richard B , Dellinger Barry , Cormier Stephania A 
Published: April 2009

AbstractBackgroundCombustion generated particulate matter is deposited in the respiratory tract and pose a hazard to the lungs through their potential to cause oxidative stress and inflammation. We have previously shown that combustion of fuels and chlorinated hydrocarbons produce semiquinone-type radicals that are stabilized on particle surfaces (i.e. environmentally persistent free radicals; EPFRs). Because the composition and properties of actual combustion-generated particles are complex, heterogeneous in origin, and vary from day-to-day, we have chosen to use surrogate particle systems. In particular, we have chosen to use the radical of 2-monochlorophenol (MCP230) as the EPFR because we have previously shown that it forms a EPFR on Cu(II)O surfaces and catalyzes formation of PCDD/F. To understand the physicochemical properties responsible for the adverse pulmonary effects of combustion by-products, we have exposed human bronchial epithelial cells (BEAS-2B) to MCP230 or the CuO/silica substrate. Our general hypothesis was that the EPFR-containing particle would have greater toxicity than the substrate species.ResultsExposure of BEAS-2B cells to our combustion generated particle systems significantly increased reactive oxygen species (ROS) generation and decreased cellular antioxidants resulting in cell death. Resveratrol treatment reversed the decline in cellular glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels for both types of combustion-generated particle systems.ConclusionThe enhanced cytotoxicity upon exposure to MCP230 correlated with its ability to generate more cellular oxidative stress and concurrently reduce the antioxidant defenses of the epithelial cells (i.e. reduced GSH, SOD activity, and GPx). The EPFRs in MCP230 also seem to be of greater biological concern due to their ability to induce lipid peroxidation. These results are consistent with the oxidizing nature of the CuO/silica ultrafine particles and the reducing nature and prolonged environmental and biological lifetimes of the EPFRs in MCP230.
Promotion of Human Trophoblasts Invasion by Gonadotropin-Releasing Hormone (GnRH) I and GnRH II via Distinct Signaling Pathways
Authors: Liu Jing , MacCalman Colin D. , Wang Yan-ling , Leung Peter C. K. 
Published: April 2009

AbstractThe potential roles of GnRH I and GnRH II have been assigned in promoting the invasive capacity of human trophoblasts by regulating matrix metalloproteinases-2 and -9, type I tissue inhibitor of matrix metalloproteinase, and urokinase plasminogen activator/plasminogen activator inhibitor protease systems during human placentation, and GnRH II has been shown to be more potent than GnRH I. However, the mechanisms for the differential effects of these two hormones remain unclear. In this study, we examined the invasion-promoting effects and the signaling pathways of GnRH I and GnRH II in human trophoblasts. The data revealed that both GnRH I and GnRH II were key autocrine and/or paracrine regulators in facilitating trophoblast invasion. The GnRH receptor antagonist (Antide) and specific small interfering RNA for GnRH receptor inhibited the regulatory effects of GnRH I, but not GnRH II, on trophoblast invasion. Both GnRH I and II activated protein kinase C, ERK1/2, and c-Jun N-terminal kinase to mediate their effects on trophoblast invasion, whereas only GnRH II elicited invasion-promoting action through transactivating the tyrosine kinase activity of epidermal growth factor receptor in trophoblasts. Our observations elucidate a ligand-dependent selective cross-communication between GnRH receptor and epidermal growth factor receptor signaling systems in human trophoblastic cell, and this would further our understanding on the differentially biological significance of these two forms of GnRH in extrapituitary tissues.
Minireview: The Case for Obesogens
Authors: Grün Felix , Blumberg Bruce 
Published: April 2009

AbstractObesity and obesity-related disorders, such as type 2 diabetes, hypertension, and cardiovascular disease, are epidemic in Western countries, particularly the United States. The conventional wisdom holds that obesity is primarily the result of a positive energy balance, i.e. too many calories in and too few calories burned. Although it is self-evident that fat cannot be accumulated without a higher caloric intake than expenditure, recent research in a number of laboratories suggests the existence of chemicals that alter regulation of energy balance to favor weight gain and obesity. These obesogens derail the homeostatic mechanisms important for weight control, such that exposed individuals are predisposed to weight gain, despite normal diet and exercise. This review considers the evidence for obesogens, how they might act, and where future research is needed to clarify their relative contribution to the obesity epidemic.
Endogenous Betaglycan Is Essential for High-Potency Inhibin Antagonism in Gonadotropes
Authors: Wiater Ezra , Lewis Kathy A. , Donaldson Cynthia , Vaughan Joan , Bilezikjian Louise , Vale Wylie 
Published: April 2009

Abstract
Inhibins are endocrine hormones that regulate gametogenesis and reproduction through a negative feedback loop with FSH. Inhibin action involves antagonism of signaling by activin or other TGFβ family ligands. In transfection assays, antagonism by inhibin can be potentiated by betaglycan, a coreceptor for selected TGFβ family ligands. We tested whether betaglycan is an obligate inhibin coreceptor through disruption of betaglycan function by RNA interference-mediated knockdown and immunoneutralization. Betaglycan knockdown and anti-betaglycan IgG each independently prevented inhibin-A binding to betaglycan and reversed functional effects of transfected betaglycan. Neither betaglycan immunoneutralization nor knockdown affected activin responsiveness in cell lines or in rat anterior pituitary cultures. Betaglycan knockdown decreased the potency of inhibin antagonism of activin-induced FSH secretion in primary gonadotropes. Similarly, anti-betaglycan IgG decreased the potency of inhibin antagonism in primary gonadotropes in a dose-dependent manner, with a reduction in the sensitivity to inhibin-A of greater than 1000-fold. These data establish that betaglycan is an endogenous inhibin coreceptor required for high-sensitivity inhibin antagonism of activin signaling in rat anterior pituitary gonadotropes.
Atmospheric oxygen level affects growth trajectory, cardiopulmonary allometry and metabolic rate in the American alligator (Alligator mississippiensis)
Authors: Owerkowicz Tomasz , Elsey Ruth M. , Hicks James W. 
Published: April 2009

SUMMARYRecent palaeoatmospheric models suggest large-scale fluctuations in ambient oxygen level over the past 550 million years. To better understand how global hypoxia and hyperoxia might have affected the growth and physiology of contemporary vertebrates, we incubated eggs and raised hatchlings of the American alligator. Crocodilians are one of few vertebrate taxa that survived these global changes with distinctly conservative morphology. We maintained animals at 30°C under chronic hypoxia (12% O2), normoxia (21%O2) or hyperoxia (30% O2). At hatching, hypoxic animals were significantly smaller than their normoxic and hyperoxic siblings. Over the course of 3 months, post-hatching growth was fastest under hyperoxia and slowest under hypoxia. Hypoxia, but not hyperoxia, caused distinct scaling of major visceral organs–reduction of liver mass, enlargement of the heart and accelerated growth of lungs. When absorptive and post-absorptive metabolic rates were measured in juvenile alligators, the increase in oxygen consumption rate due to digestion/absorption of food was greatest in hyperoxic alligators and smallest in hypoxic ones. Hyperoxic alligators exhibited the lowest breathing rate and highest oxygen consumption per breath. We suggest that,despite compensatory cardiopulmonary remodelling, growth of hypoxic alligators is constrained by low atmospheric oxygen supply, which may limit their food utilisation capacity. Conversely, the combination of elevated metabolism and low cost of breathing in hyperoxic alligators allows for a greater proportion of metabolised energy to be available for growth. This suggests that growth and metabolic patterns of extinct vertebrates would have been significantly affected by changes in the atmospheric oxygen level.
Circannual basis of geographically distinct bird schedules
Authors: Helm Barbara , Schwabl Ingrid , Gwinner Eberhard 
Published: April 2009

SUMMARYTo anticipate seasonal change, organisms schedule their annual activities by using calendrical cues like photoperiod. The use of cues must be fitted to local conditions because schedules differ between species and habitats. In complete absence of temporal information, many species show persistent circannual cycles that are synchronised, but not driven, by photoperiod. The contribution of circannual rhythms to timing under natural photoperiodic conditions is still unclear. In a suite of experiments, we examined timing in two closely related songbirds (Siberian and European stonechats) that inhabit similar latitudes but differ in seasonal behaviour. Under a more continental climate, Siberian stonechats breed later, moult faster and migrate further than European stonechats. We tested hypotheses for seasonal timing mechanisms by comparing the birds under constant and naturally changing daylengths. The taxa retained characteristic reproductive and moult schedules and hybrids behaved roughly intermediately. Based on their distinct circannual cycles, we expected European and Siberian stonechats to differ in photoperiodic responses at a given time of year. We found that the taxa responded, as predicted, in opposite ways to photoperiodic simulations as experienced on different migration routes. The findings indicate that circannual rhythms reflect geographically distinct periodic changes in seasonal disposition and cue-response mechanisms. Under natural daylengths, the phase relationship of the underlying circannual rhythm to the external year determines the action of photoperiod. Circannual rhythms are widespread among long-lived species. Accordingly, responses to environmental change, range expansion and novel migration patterns may depend on the particulars of a species' underlying circannual programming.
Adaptive echolocation behavior in bats for the analysis of auditory scenes
Authors: Chiu Chen , Xian Wei , Moss Cynthia F. 
Published: April 2009

SUMMARY
Echolocating bats emit sonar pulses and listen to returning echoes to probe their surroundings. Bats adapt their echolocation call design to cope with dynamic changes in the acoustic environment, including habitat change or the presence of nearby conspecifics/heterospecifics. Seven pairs of big brown bats, Eptesicus fuscus, were tested in this study to examine how they adjusted their echolocation calls when flying and competing with a conspecific for food. Results showed that differences in five call parameters, start/end frequencies, duration, bandwidth and sweep rate, significantly increased in the two-bat condition compared with the baseline data. In addition, the magnitude of spectral separation of calls was negatively correlated with the baseline call design differences in individual bats. Bats with small baseline call frequency differences showed larger increases in call frequency separation when paired than those with large baseline call frequency differences, suggesting that bats actively change their sonar call structure if pre-existing differences in call design are small. Call design adjustments were also influenced by physical spacing between two bats. Calls of paired bats exhibited the largest design separations when inter-bat distance was shorter than 0.5 m, and the separation decreased as the spacing increased. All individuals modified at least one baseline call parameter in response to the presence of another conspecific. We propose that dissimilarity between the time–frequency features of sonar calls produced by different bats aids each individual in segregating echoes of its own sonar vocalizations from the acoustic signals of neighboring bats.