bluuebunny/crossref_metadata_2025 huggingface dataset:
Work Disability, Mortgage Default, and Life Satisfaction in the Economic Downturn
Authors: Huang Jin
Published: June 2011

The study examined the relationship between work disability and mortgage default in the latest economic downturn in the United States and further assessed the associations of work disability and mortgage default with life satisfaction. Work disability was measured by self-reported health-related work limitations. Mortgage default was defined as delaying home mortgage payment for more than 30 days in the study. The data were obtained from the 2007 and 2009 Panel Study of Income Dynamics, and logistic regression was used to test research questions. Of the 2,361 homeowners who had a mortgage, nearly 6% had mortgage default in 2009, and 14.5% of householders or their spouses had work disabilities in 2007. The disability group was significantly more likely than the non-disability group to have mortgage default, AOR = 1.80, 95% CI = (1.02, 3.16). Both work disability and mortgage default had significant and negative associations with life satisfaction. Results suggest that mortgage assistance services should be provided for individuals with work disabilities and their families to prevent housing distress and improve quality of life.
Comparison of Control Laws for Vibration Suppression Based on Energy Consumption
Authors: Ya Wang  , Inman Daniel J.
Published: June 2011

The research study presented here examines four conventional vibration suppression control laws and four hybrid modifications of these laws using a switching method. The motivation is to determine which of these eight controllers results in the least amount of power flow to the actuator to have the same settling time under free vibrations. The reason to look at reduced energy controllers is the idea that in some applications, very little energy is available for control, yet passive and semi-active methods cannot meet performance demands. In particular, the eventual goal is to reduce transient vibrations of smart structures using energy obtained from harvesting and/or low-power storage devices (batteries or super capacitors), as often desirable in aerospace systems. The four conventional active control systems compared in this study are Positive Position Feedback (PPF) control, Proportional Integral Derivative (PID) control, non-linear control, and Linear Quadratic Regulator (LQR) controls. A hybrid version of each controller is obtained by implementing a bang-bang control law (on-off control). The bang-bang control algorithm switches the control voltage between an external voltage supply and the feedback signal provided by the PPF, PID, non-linear, or LQR controllers. The purpose of combining the bang-bang control law with the aforementioned controllers is to reduce the power requirement for vibration suppression by providing an active controller with limited voltage input. Free vibrations of a thin cantilevered beam with a piezoceramic transducer are controlled by these eight controllers with a focus on the fundamental transverse vibration mode. Experimental results exhibit that the system with hybrid bang-bang-non-linear controller requires 67.3% less power than its conventional version. The hybrid versions require significantly less power flow compared to their conventional counterparts for the PPF, PID, and LQR controllers as well. Experiments also reveal the presence of substantial piezoelectric non-linearities in the transducer. The voltage-dependent behavior of the electromechanical coupling coefficient is identified empirically and represented by a curve-fit expression. A real-time adaptive control algorithm is developed to account for the voltage-dependent behavior of the coupling coefficient, enabling good agreement between the simulation and experimental results.
Patient Reactions to Vital Sign Measures
Authors: Shea Kimberly , Chamoff Breanna
Published: June 2011

Increasingly home health agencies are using home-based technologies to monitor vital signs of chronically ill patients. Patients receive measurements such as blood pressure and weight that indicate risks to their health. Cognitive reactions to risk measures have been studied for face-to-face delivery; however, it is unknown whether the same reactions exist with technology delivery. Reported in this article are study results of a comparative content expert analysis of reactions to technology-delivered health-risk measures. Results suggest that patients have the similar reactions but may be more likely to just accept, without evaluating or considering threats to their health. As home telemonitoring applications continue to evolve, care must be taken avoid creating passive patients and develop best practices that use technology to encourage beneficial self-care behaviors.
Exploring the Necessary Conditions for Evaluation Use in Program Change
Authors: Ledermann Simone
Published: June 2011

Research has identified a wide range of factors that affect evaluation use but continues to be inconclusive as to their relative importance. This article addresses the complex phenomenon of evaluation use in three ways: first, it draws on recent conceptual developments to delimitate the examined form of use; second, it aims at identifying conditions that are necessary but not necessarily sufficient for evaluation use; third, it combines mechanisms of evaluation use, context conditions, and actor perceptions. The study reported here examines the use of 11 program and project evaluations by the Swiss Agency for Development and Cooperation (SDC). The article makes use of qualitative comparative analysis (QCA), a method that is well suited to the study of context-bound necessity. It is concluded that the analysis of conditions that are necessary to trigger mechanisms of evaluation use in certain contexts is challenging, but promising to face the complexity of the phenomenon.
Investigation of fretting fatigue behaviour under multiaxial non-proportional loading
Authors: Liu B , He G , Jiang X , Zhu M
Published: June 2011

Fretting fatigue is a structural mechanism observed when two contacting bodies are subjected to an oscillatory loading. The study on fretting fatigue behaviour of 60Si2Mn steel was conducted under condition of multiaxial non-proportional loading. The fretting fatigue lives corresponding to different cyclic axial stress amplitudes were tested with same rotation loading amplitude and contact normal pressure. The characters of frictional and wear surfaces and fracture morphology were analysed in detail by scanning electron microscopy and optical images. It is found the fretting fatigue life decreases but the work done by axial frictional force increases with the increase of the axial stress amplitude. Fretting fatigue crack initiates near the trailing edge of fretting contact zone and propagates at an angle of 45° along the axial direction at the existence of tangential shear stress produced by the rotation loading. Apparently, the fracture surface is not smooth and perpendicular to the axial direction of specimen.
Campus Press, Inc.: A critical analysis of the corporatization of collegiate media
Authors: Corrigan Thomas F , Proffitt Jennifer M
Published: June 2011

This article examines the corporatization of collegiate media in the United States. Gannett Company, Inc.’s purchase of two university publications, the FSView & Florida Flambeau ( FSView) at Florida State University and the Central Florida Future at the University of Central Florida, have raised concerns regarding the autonomy of the campus press. This article first defines the functions and structures of the campus press and how each contribute to the normative goals and democratic potential of collegiate student newspapers. The article goes on to argue that a corporate ownership structure, despite the alluring rhetoric espoused by corporate media, meets the needs of advertisers and shareholders, not the communities the campus press should serve. Gannett’s purchase of the FSView is examined in depth because it provides a revealing case study of the underlying interests that corporations such as Gannett have in collegiate media.
Evaluating newspaper performance in the public sphere: Press accounts of Westminster elections in Scotland and in England in the early post-devolution period
Authors: Dekavalla Marina
Published: June 2011

This article explores ways of evaluating the performance of the press in an electoral public sphere and compares the output of newspapers in England and in Scotland during the 2001 and 2005 general election campaigns. It combines content analysis with critical discussion of examples of coverage and complements these with evidence from interviews with Scottish political editors. It argues that, even though Scottish newspapers gave less coverage to the two elections than titles sold in England, both sets of newspapers performed better in their role as providers of information and opinion to inform the electorate, than in that of presenting an inclusive, discursive and diverse electoral debate or encouraging forms of active citizenry.
The South is talking back: With a white face and a British accent – editorial dilemmas in Al Jazeera English
Authors: Ustad Figenschou Tine
Published: June 2011

The production level has been neglected in current scholarship on global news contra-flows. Al Jazeera English (AJE) is a resourceful, multi-newsroom satellite news channel with an ambitious, alternative editorial agenda that poses practical challenges and conflicts. Based on 35 qualitative interviews with channel management and editorial members of staff, document analysis and observation of editorial meetings, the present article examines the employees’ reflections on these challenges during its first years on air. It problematizes the extent to which AJE should follow the western-led mainstream news cycle as opposed to creating an alternative agenda. Furthermore, discussions about who should be invited to represent ‘the other’ opinion among AJE’s news sources reveal diverging sourcing strategies and conflicting conceptions of which opinions should be represented on the channel. These dilemmas are symptoms of the structural contradictions in the AJE project aiming to implement an alternative, southern news perspective while maintaining professional journalistic standards. 1
The language of the press in Soviet and post-Soviet Russia: Creation of the citizen role through newspaper discourse
Authors: von Seth Rutger
Published: June 2011

The Russian media system was during most of the 20th century part of the state institutions. During glasnost and perestroika, the media became gradually more independent of the state. However, the subsequent apex of journalistic freedom in the late 1980s and the early 1990s was followed by stagnation and a pronounced democratic setback following Putin’s accession to power. Despite this, the findings based on qualitative text analysis of articles in the daily press strongly indicate that after 1991 readers of the press are being increasingly addressed as active and knowledgeable citizens, a tendency which is strengthened during the entire period of study. Methods for text examination are speech act and modality analysis, exploring how readers are discursively positioned in the sample text material, which covers the democratically critical time span 1978–2003. The findings imply that although post-Soviet journalism itself faces considerable difficulties, a firm cultural ground for citizen participation in society has been laid through changes in press language.
An experimental study of unsteady hydrodynamics of a single scull
Authors: Day A H , Campbell I , Clelland D , Cichowicz J
Published: June 2011

The effect of hull dynamics on the hydrodynamic performance of a single scull is investigated via a combination of field trials and tank tests. The location of laminar-turbulent transition in unsteady flow is explored via several series of hot-film measurements on the bow of a full-scale single scull in unsteady flow in both towing tank and field-trial conditions. Results demonstrate that the measured real-world viscous-flow behaviour can be successfully reproduced in the tank using an oscillating sub-carriage to reproduce the surging motion measured in the field trials. It can be seen that there is a strong link between turbulence and acceleration; results show that the link is relatively insensitive to mean velocity, but that small changes in acceleration time-histories can have a marked effect, as can the presence of small waves.

The impact of the location of laminar turbulent transition is investigated by way of a series of resistance tests, both with free transition and with transition forced by turbulence stimulation at two different locations. Results indicate that an aft movement of 200 mm of the location of transition can reduce resistance by almost 0.5 per cent. Unsteady tests using the oscillating sub-carriage indicate that unsteady effects add around 3 per cent to the total mean resistance with free transition.
The relationship between bone, hemopoietic stem cells, and vasculature
Authors: Ellis Sarah L. , Grassinger Jochen , Jones Allan , Borg Judy , Camenisch Todd , Haylock David , Bertoncello Ivan , Nilsson Susan K.
Published: June 2011

A large body of evidence suggests hemopoietic stem cells (HSCs) exist in an endosteal niche close to bone, whereas others suggest that the HSC niche is intimately associated with vasculature. In this study, we show that transplanted hemopoietic stem and progenitor cells (HSPCs) home preferentially to the trabecular-rich metaphysis of the femurs in nonablated mice at all time points from 15 minutes to 15 hours after transplantation. Within this region, they exist in an endosteal niche in close association with blood vessels. The preferential homing of HSPCs to the metaphysis occurs rapidly after transplantation, suggesting that blood vessels within this region may express a unique repertoire of endothelial adhesive molecules. One candidate is hyaluronan (HA), which is highly expressed on the blood vessel endothelium in the metaphysis. Analysis of the early stages of homing and the spatial dis-tribution of transplanted HSPCs at the single-cell level in mice devoid of Has3-synthesized HA, provides evidence for a previously undescribed role for HA expressed on endothelial cells in directing the homing of HSPCs to the metaphysis.
DC-like cell-dependent activation of human natural killer cells by the bisphosphonate zoledronic acid is regulated by γδ T lymphocytes
Authors: Nussbaumer Oliver , Gruenbacher Georg , Gander Hubert , Thurnher Martin
Published: June 2011

Bisphosphonates are mainly used for the inhibition of osteoclast-mediated bone resorption but also have been shown to induce γδ T-cell activation. Using IL-2–primed cultures of CD56+ peripheral blood mononuclear cells, we show here that zoledronic acid (zoledronate) could induce IFN-γ production not only in γδ T lymphocytes but, surprisingly, also in natural killer (NK) cells in a manner that depended on antigen-presenting cells, which share properties of inflammatory monocytes and dendritic cells (DCs; here referred to as DC-like cells). In the presence of γδ T lymphocytes, DC-like cells were rapidly eliminated, and NK cell IFN-γ production was silenced. Conversely, in the absence of γδ T lymphocytes, DC-like cells were spared, allowing NK cell IFN-γ production to proceed. γδ T cell–independent NK cell activation in response to zoledronate was because of downstream depletion of endogenous prenyl pyrophosphates and subsequent caspase-1 activation in DC-like cells, which then provide mature IL-18 and IL-1β for the activation of IL-2–primed NK cells. Pharmacologic inhibition of caspase-1 almost abolished IFN-γ production in NK cells and γδ T lymphocytes, indicating that caspase-1–mediated cytokine maturation is the crucial mechanism underlying innate lymphocyte activation in response to zoledronate.
Cytotoxicity of farnesyltransferase inhibitors in lymphoid cells mediated by MAPK pathway inhibition and Bim up-regulation
Authors: Ding Husheng , Hackbarth Jennifer , Schneider Paula A. , Peterson Kevin L. , Meng X. Wei , Dai Haiming , Witzig Thomas E. , Kaufmann Scott H.
Published: June 2011

The mechanism of cytotoxicity of farnesyltransferase inhibitors is incompletely understood and seems to vary depending on the cell type. To identify potential determinants of sensitivity or resistance for study in the accompanying clinical trial (Witzig et al, page 4882), we examined the mechanism of cytotoxicity of tipifarnib in human lymphoid cell lines. Based on initial experiments showing that Jurkat variants lacking Fas-associated death domain or procaspase-8 undergo tipifarnib-induced apoptosis, whereas cells lacking caspase-9 or overexpressing Bcl-2 do not, we examined changes in Bcl-2 family members. Tipifarnib caused dose-dependent up-regulation of Bim in lymphoid cell lines (Jurkat, Molt3, H9, DoHH2, and RL) that undergo tipifarnib-induced apoptosis but not in lines (SKW6.4 and Hs445) that resist tipifarnib-induced apoptosis. Further analysis demonstrated that increased Bim levels reflect inhibition of signaling from c-Raf to MEK1/2 and ERK1/2. Additional experiments showed that down-regulation of the Ras guanine nucleotide exchange factor RasGRP1 diminished tipifarnib sensitivity, suggesting that H-Ras or N-Ras is a critical farnesylation target upstream of c-Raf in lymphoid cells. These results not only trace a pathway through c-Raf to Bim that contributes to tipifarnib cytotoxicity in human lymphoid cells but also identify potential determinants of sensitivity to this agent.
Novel adoptive T-cell immunotherapy using a WT1-specific TCR vector encoding silencers for endogenous TCRs shows marked antileukemia reactivity and safety
Authors: Ochi Toshiki , Fujiwara Hiroshi , Okamoto Sachiko , An Jun , Nagai Kozo , Shirakata Toshiaki , Mineno Junichi , Kuzushima Kiyotaka , Shiku Hiroshi , Yasukawa Masaki
Published: June 2011

Adoptive T-cell therapy for malignancies using redirected T cells genetically engineered by tumor antigen-specific T-cell receptor (TCR) gene transfer is associated with mispairing between introduced and endogenous TCR chains with unknown specificity. Therefore, deterioration of antitumor reactivity and serious autoimmune reactivity are major concerns. To address this problem, we have recently established a novel retroviral vector system encoding siRNAs for endogenous TCR genes (siTCR vector). In this study, to test the clinical application of siTCR gene therapy for human leukemia, we examined in detail the efficacy and safety of WT1-siTCR–transduced T cells. Compared with conventional WT1-TCR (WT1-coTCR) gene-transduced T cells, these cells showed significant enhancement of antileukemia reactivity resulting from stronger expression of the introduced WT1-specific TCR with inhibition of endogenous TCRs. Notably, WT1-siTCR gene-transduced T cells were remarkably expandable after repetitive stimulation with WT1 peptide in vitro, without any deterioration of antigen specificity. WT1-siTCR gene–transduced T cells from leukemia patients successfully lysed autologous leukemia cells, but not normal hematopoietic progenitor cells. In a mouse xenograft model, adoptively transferred WT1-siTCR gene-transduced T cells exerted distinct antileukemia efficacy but did not inhibit human hematopoiesis. Our results suggest that gene-immunotherapy for leukemia using this WT1-siTCR system holds considerable promise.
Erg is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice
Authors: Ng Ashley P. , Loughran Stephen J. , Metcalf Donald , Hyland Craig D. , de Graaf Carolyn A. , Hu Yifang , Smyth Gordon K. , Hilton Douglas J. , Kile Benjamin T. , Alexander Warren S.
Published: June 2011

Hematopoietic stem cells (HSCs) are rare residents of the bone marrow responsible for the lifelong production of blood cells. Regulation of the balance between HSC self-renewal and differentiation is central to hematopoiesis, allowing precisely regulated generation of mature blood cells at steady state and expanded production at times of rapid need, as well as maintaining ongoing stem cell capacity. Erg, a member of the Ets family of transcription factors, is deregulated in cancers; and although Erg is known to be required for regulation of adult HSCs, its precise role has not been defined. We show here that, although heterozygosity for functional Erg is sufficient for adequate steady-state HSC maintenance, Erg+/Mld2 mutant mice exhibit impaired HSC self-renewal after bone marrow transplantation or during recovery from myelotoxic stress. Moreover, although mice functionally compromised for either Erg or Mpl, the receptor for thrombopoietin, a key regulator of HSC quiescence, maintained sufficient HSC activity to sustain hematopoiesis, Mpl−/−Erg+/Mld2 compound mutant mice displayed exacerbated stem cell deficiencies and bone marrow failure. Thus, Erg is a critical regulator of adult HSCs, essential for maintaining self-renewal at times of high HSC cycling.
Bcl-xL–inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets
Authors: Schoenwaelder Simone M. , Jarman Kate E. , Gardiner Elizabeth E. , Hua My , Qiao Jianlin , White Michael J. , Josefsson Emma C. , Alwis Imala , Ono Akiko , Willcox Abbey , Andrews Robert K. , Mason Kylie D. , Salem Hatem H. , Huang David C. S. , Kile Benjamin T. , Roberts Andrew W. , Jackson Shaun P.
Published: June 2011

BH3 mimetics are a new class of proapo-ptotic anticancer agents that have shown considerable promise in preclinical animal models and early-stage human trials. These agents act by inhibiting the pro-survival function of one or more Bcl-2–related proteins. Agents that inhibit Bcl-xL induce rapid platelet death that leads to thrombocytopenia; however, their impact on the function of residual circulating platelets remains unclear. In this study, we demonstrate that the BH3 mimetics, ABT-737 or ABT-263, induce a time- and dose-dependent decrease in platelet adhesive function that correlates with ectodomain shedding of the major platelet adhesion receptors, glycoprotein Ibα and glycoprotein VI, and functional down-regulation of integrin αIIbβ3. Analysis of platelets from mice treated with higher doses of BH3 mimetics revealed the presence of a subpopulation of circulating platelets undergoing cell death that have impaired activation responses to soluble agonists. Functional analysis of platelets by intravital microscopy revealed a time-dependent defect in platelet aggregation at sites of vascular injury that correlated with an increase in tail bleeding time. Overall, these studies demonstrate that Bcl-xL–inhibitory BH3 mimetics not only induce thrombocytopenia but also a transient thrombocytopathy that can undermine the hemostatic function of platelets.
Efficacy of retreatment with immunomodulatory drugs (IMiDs) in patients receiving IMiDs for initial therapy of newly diagnosed multiple myeloma
Authors: Madan Sumit , Lacy Martha Q. , Dispenzieri Angela , Gertz Morie A. , Buadi Francis , Hayman Suzanne R. , Detweiler-Short Kristen , Dingli David , Zeldenrust Steven , Lust John , Greipp Philip R. , Rajkumar S. Vincent , Kumar Shaji
Published: June 2011

The efficacy of retreatment with immunomodulatory drugs (IMiDs) among patients with multiple myeloma who received this class of drugs for initial therapy is unknown. We studied 140 patients who received either thalidomide-dexamethasone (81; 58%) or lenalidomide-dexamethasone (59; 42%) as first-line therapy of multiple myeloma followed by repeat IMiD (thalidomide [34; 24%] or lenalidomide [106; 76%]) as one of the salvage regimens. A median of 2 treatments (range, 1-6), including a stem cell transplant in 105 patients (75%), were administered before IMiD-based salvage therapy. The median time from diagnosis to repeat exposure to IMiD was 28 months. Among the 113 evaluable patients, 50 (44%) achieved at least a partial response, and 63 (56%) achieved less than a partial response to repeat IMiD. Response rates with lenalidomide retreatment were higher than with repeat administration of thalidomide.
Stanniocalcin-1 promotes tumor angiogenesis through up-regulation of VEGF in gastric cancer cells
Authors: He Ling-fang , Wang Ting-ting , Gao Qian-ying , Zhao Guang-feng , Huang Ya-hong , Yu Li-ke , Hou Ya-yi
Published: June 2011

Background

Stanniocalcin-1(STC-1) is up-regulated in several cancers including gastric cancer. Evidences suggest that STC-1 is associated with carcinogenesis and angiogenic process. However, it is unclear on the exact role for STC-1 in inducing angiogenesis and tumorigeneisis.

Method

BGC/STC cells (high-expression of STC-1) and BGC/shSTC cells (low- expression of STC-1) were constructed to investigate the effect of STC-1 on the xenograft tumor growth and angiogenesis in vitro and in vivo. ELISA assay was used to detect the expression of vascular endothelial growth factor (VEGF) in the supernatants. Neutralizing antibody was used to inhibit VEGF expression in supernatants. The expression of phosphorylated -PKCβII, phosphorylated -ERK1/2 and phosphorylated -P38 in the BGC treated with STC-1protein was detected by western blot.

Results

STC-1 could promote angiogenesis in vitro and in vivo, and the angiogenesis was consistent with VEGF expression in vitro. Inhibition of VEGF expression in supernatants with neutralizing antibody markedly abolished angiogenesis induced by STC-1 in vitro. The process of STC-1-regulated VEGF expression was mediated via PKCβII and ERK1/2.

Conclusions

STC-1 promotes the expression of VEGF depended on the activation of PKCβII and ERK1/2 pathways. VEGF subsequently enhances tumor angiogenesis which in turn promotes the gastric tumor growth.
Weight and metabolic effects of cpap in obstructive sleep apnea patients with obesity
Authors: Garcia Jose M , Sharafkhaneh Hossein , Hirshkowitz Max , Elkhatib Rania , Sharafkhaneh Amir
Published: June 2011

Background

Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.

Methods

In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.

Results

CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.

Conclusions

Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.
SOX10 directly modulates ERBB3 transcription via an intronic neural crest enhancer
Authors: Prasad Megana K , Reed Xylena , Gorkin David U , Cronin Julia C , McAdow Anthony R , Chain Kristopher , Hodonsky Chani J , Jones Erin A , Svaren John , Antonellis Anthony , Johnson Stephen L , Loftus Stacie K , Pavan William J , McCallion Andrew S
Published: June 2011

Background

The ERBB3 gene is essential for the proper development of the neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in the progressive restriction and specification of NC derived lineages during development. However, little is known about the sequences mediating transcriptional regulation of ERBB3 or the factors that bind them.

Results

In this study we identified three transcriptional enhancers at the ERBB3 locus and evaluated their regulatory potential in vitro in NC-derived cell types and in vivo in transgenic zebrafish. One enhancer, termed ERBB3_MCS6, which lies within the first intron of ERBB3, directs the highest reporter expression in vitro and also demonstrates epigenetic marks consistent with enhancer activity. We identify a consensus SOX10 binding site within ERBB3_MCS6 and demonstrate, in vitro, its necessity and sufficiency for the activity of this enhancer. Additionally, we demonstrate that transcription from the endogenous Erbb3 locus is dependent on Sox10. Further we demonstrate in vitro that Sox10 physically interacts with that ERBB3_MCS6. Consistent with its in vitro activity, we also show that ERBB3_MCS6 drives reporter expression in NC cells and a subset of its derivative lineages in vivo in zebrafish in a manner consistent with erbb3b expression. We also demonstrate, using morpholino analysis, that Sox10 is necessary for ERBB3_MCS6 expression in vivo in zebrafish.

Conclusions

Taken collectively, our data suggest that ERBB3 may be directly regulated by SOX10, and that this control may in part be facilitated by ERBB3_MCS6.
The Drosophila Netrin receptor frazzled/DCC functions as an invasive tumor suppressor
Authors: VanZomeren-Dohm Adrienne , Sarro Joseph , Flannery Ellen , Duman-Scheel Molly
Published: June 2011

Background

Loss of heterozygosity at 18q, which includes the Deleted in Colorectal Cancer (DCC) gene, has been linked to many human cancers. However, it is unclear if loss of DCC is the specific underlying cause of these cancers. The Drosophila imaginal discs are excellent systems in which to study DCC function, as it is possible to model human tumors through the generation of somatic clones of cells bearing multiple genetic lesions. Here, these attributes of the fly system were utilized to investigate the potential tumor suppressing functions of the Drosophila DCC homologue frazzled (fra) during eye-antennal disc development.

Results

Most fra loss of function clones are eliminated during development. However, when mutant clone cells generated in the developing eye were rescued from death, partially differentiated eye cells were found outside of the normal eye field, and in extreme cases distant sites of the body. Characterization of these cells during development indicates that fra mutant cells display characteristics of invasive tumor cells, including increased levels of phospho-ERK, phospho-JNK, and Mmp-1, changes in cadherin expression, remodeling of the actin cytoskeleton, and loss of polarity. Mutation of fra promotes basement membrane degradation and invasion which are repressed by inhibition of Rho1 signaling. Although inhibition of JNK signaling blocks invasive phenotypes in some metastatic cancer models in flies, blocking JNK signaling inhibits fra mutant cell death, thereby enhancing the fra mutant phenotype.

Conclusions

The results of this investigation provide the first direct link between point mutations in fra/DCC and metastatic phenotypes in an animal model and suggest that Fra functions as an invasive tumor suppressor during Drosophila development.
Convergent and parallel evolution in life habit of the scallops (Bivalvia: Pectinidae)
Authors: Alejandrino Alvin , Puslednik Louise , Serb Jeanne M
Published: June 2011

Background

We employed a phylogenetic framework to identify patterns of life habit evolution in the marine bivalve family Pectinidae. Specifically, we examined the number of independent origins of each life habit and distinguished between convergent and parallel trajectories of life habit evolution using ancestral state estimation. We also investigated whether ancestral character states influence the frequency or type of evolutionary trajectories.

Results

We determined that temporary attachment to substrata by byssal threads is the most likely ancestral condition for the Pectinidae, with subsequent transitions to the five remaining habit types. Nearly all transitions between life habit classes were repeated in our phylogeny and the majority of these transitions were the result of parallel evolution from byssate ancestors. Convergent evolution also occurred within the Pectinidae and produced two additional gliding clades and two recessing lineages. Furthermore, our analysis indicates that byssal attaching gave rise to significantly more of the transitions than any other life habit and that the cementing and nestling classes are only represented as evolutionary outcomes in our phylogeny, never as progenitor states.

Conclusions

Collectively, our results illustrate that both convergence and parallelism generated repeated life habit states in the scallops. Bias in the types of habit transitions observed may indicate constraints due to physical or ontogenetic limitations of particular phenotypes.
Immunoglobulin heavy chains in medaka (Oryzias latipes)
Authors: Magadán-Mompó Susana , Sánchez-Espinel Christian , Gambón-Deza Francisco
Published: June 2011

Background

Bony fish present an immunological system, which evolved independently from those of animals that migrated to land 400 million years ago. The publication of whole genome sequences and the availability of several cDNA libraries for medaka (Oryzias latipes) permitted us to perform a thorough analysis of immunoglobulin heavy chains present in this teleost.

Results

We identified IgM and IgD coding ESTs, mainly in spleen, kidney and gills using published cDNA libraries but we did not find any sequence that coded for IgT or other heavy chain isotypes described in fish. The IgM - ESTs corresponded with the secreted and membrane forms and surprisingly, the latter form only presented two constant heavy chain domains. This is the first time that this short form of membrane IgM is described in a teleost. It is different from that identified in Notothenioid teleost because it does not present the typical splicing pattern of membrane IgM. The identified IgD-ESTs only present membrane transcripts, with Cμ1 and five Cδ exons. Furthermore, there are ESTs with sequences that do not have any VH which disrupt open reading frames.

A scan of the medaka genome using transcripts and genomic short reads resulted in five zones within a region on chromosome 8 with Cμ and Cδ exons. Some of these exons do not form part of antibodies and were at times interspersed, suggesting a recombination process between zones. An analysis of the ESTs confirmed that no antibodies are expressed from zone 3.

Conclusions

Our results suggest that the IGH locus duplication is very common among teleosts, wherein the existence of a recombination process explains the sequence homology between them.
Investigation of fMRI activation in the internal capsule
Authors: Gawryluk Jodie R , Mazerolle Erin L , Brewer Kimberley D , Beyea Steven D , D'Arcy Ryan CN
Published: June 2011

Background

Functional magnetic resonance imaging (fMRI) in white matter has long been considered controversial. Recently, this viewpoint has been challenged by an emerging body of evidence demonstrating white matter activation in the corpus callosum. The current study aimed to determine whether white matter activation could be detected outside of the corpus callosum, in the internal capsule. Data were acquired from a 4 T MRI using a specialized asymmetric spin echo spiral sequence. A motor task was selected to elicit activation in the posterior limb of the internal capsule.

Results

White matter fMRI activation was examined at the individual and group levels. Analyses revealed that activation was present in the posterior limb of the internal capsule in 80% of participants. These results provide further support for white matter fMRI activation.

Conclusions

The ability to visualize functionally active tracts has strong implications for the basic scientific study of connectivity and the clinical assessment of white matter disease.
Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease
Authors: Chen Xi , Xing Shihui , Feng Yanqing , Chen Songlin , Pei Zhong , Wang Chuhuai , Liang Xiuling
Published: June 2011

Background

Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx) mice.

Methods

Recipient tx mice were sublethally irradiated (5 Gy) prior to transplantation. The congenic wild-type (DL) BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age) or late stage (5 months of age) of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST) levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively.

Results

The DL BM cells population was observed from 1 to 12 weeks and peaked by the 4th week in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all P < 0.05). In contrast, BM cells transplantation during the late stage only corrected AST levels from 4 to 12 weeks post-transplant and copper accumulation at 12 weeks post-transplant (all P < 0.05). No significant difference was found between the saline and tx BM cells transplantation groups across the observed time points (P > 0.05).

Conclusions

Early stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.
Effects of aerobic exercise therapy and cognitive behavioural therapy on functioning and quality of life in amyotrophic lateral sclerosis: protocol of the FACTS-2-ALS trial
Authors: van Groenestijn Annerieke C , van de Port Ingrid GL , Schröder Carin D , Post Marcel WM , Grupstra Hepke F , Kruitwagen Esther T , van der Linde Harmen , van Vliet Reinout O , van de Weerd Margreet GH , van den Berg Leonard H , Lindeman Eline
Published: June 2011

Background

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder affecting motor neurons in the spinal cord, brainstem and motor cortex, leading to muscle weakness. Muscle weakness may result in the avoidance of physical activity, which exacerbates disuse weakness and cardiovascular deconditioning. The impact of the grave prognosis may result in depressive symptoms and hopelessness. Since there is no cure for ALS, optimal treatment is based on symptom management and preservation of quality of life (QoL), provided in a multidisciplinary setting. Two distinctly different therapeutic interventions may be effective to improve or preserve daily functioning and QoL at the highest achievable level: aerobic exercise therapy (AET) to maintain or enhance functional capacity and cognitive behavioural therapy (CBT) to improve coping style and cognitions in patients with ALS. However, evidence to support either approach is still insufficient, and the underlying mechanisms of the approaches remain poorly understood. The primary aim of the FACTS-2-ALS trial is to study the effects of AET and CBT, in addition to usual care, compared to usual care alone, on functioning and QoL in patients with ALS.

Methods / Design

A multicentre, single-blinded, randomized controlled trial with a postponed information model will be conducted. A sample of 120 patients with ALS (1 month post diagnosis) will be recruited from 3 university hospitals and 1 rehabilitation centre. Patients will be randomized to one of three groups i.e. (1) AET + usual care, (2) CBT + usual care, (3) Usual care. AET consists of a 16-week aerobic exercise programme, on 3 days a week. CBT consists of individual psychological support of patients in 5 to 10 sessions over a 16-week period. QoL, functioning and secondary outcome measures will be assessed at baseline, immediately post intervention and at 3- and 6-months follow-up.

Discussion

The FACTS-2-ALS study is the first theory-based randomized controlled trial to evaluate the effects, and the maintenance of effects, of AET and CBT on functioning and QoL in patients with ALS. The results of this study are expected to generate new evidence for the effect of multidisciplinary care of persons with ALS.

Trial registration

Dutch Trial Register NTR1616.
PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib
Authors: Wang Leiping , Zhang Qunling , Zhang Jian , Sun Si , Guo Haiyi , Jia Zhen , Wang Biyun , Shao Zhimin , Wang Zhonghua , Hu Xichun
Published: June 2011

Background

Human epidermal growth factor receptor 2 (HER2) is the most crucial ErbB receptor tyrosine kinase (RTK) family member in HER2-positive (refered to HER2-overexpressing) breast cancer which are dependent on or "addictive" to the Phosphatidylinositol-3-kinase (PI3K) pathway. HER2-related target drugs trastuzumab and lapatinib have been the foundation of treatment of HER2--positive breast cancer. This study was designed to explore the relationship between PI3K pathway activation and the sensitivity to lapatinib in HER2--positive metastatic breast cancer patients pretreated with anthracyclins, taxanes and trastuzumab.

Methods

Sixty-seven HER2-positive metastatic breast cancer patients were recruited into a global lapatinib Expanded Access Program and 57 patients have primary tumor specimens available for determination of PI3K pathway status. PTEN status was determined by immunohistochemical staining and PIK3CA mutations were detected via PCR sequencing. All patients were treated with lapatinib 1250 mg/day continuously and capecitabine 1000 mg/m2 twice daily on a 2-week-on and 1-week-off schedule until disease progression, death, withdrawal of informed consent, or intolerable toxicity.

Results

PIK3CA mutations and PTEN loss were detected in 12.3% (7/57) and 31.6% (18/57) of the patients, respectively. Twenty-two patients with PI3K pathway activation (defined as PIK3CA mutation and/or PTEN expression loss) had a lower clinical benefit rate (36.4% versus 68.6%, P = 0.017) and a lower overall response rate (9.1% versus 31.4%, P = 0.05), when compared with the 35 patients with no activation. A retrospective analysis of first trastuzumab-containing regimen treatment data showed that PI3K pathway activation correlated with a shorter median progression-free survival (4.5 versus 9.0 months, P = 0.013).

Conclusions

PIK3CA mutations occur more frequently in elder patients for HER2-positive breast cancer. PIK3CA mutations and PTEN loss are not mutually exclusive. PI3K pathway activation resulting from PTEN loss or PIK3CA mutations may lead to drug resistance to lapatinib and trastuzumab (http://ClinicalTrials.gov number, NCT00338247).
Ancient feeding ecology inferred from stable isotopic evidence from fossil horses in South America over the past 3 Ma
Authors: Prado José L , Sánchez Begoña , Alberdi María T
Published: June 2011

Background

Stable isotope ratios (13C/12C and18O/16O) in fossil teeth and bone provide key archives for understanding the ecology of extinct horses during the Plio-Pleistocene in South America; however, what happened in areas of sympatry betweenEquus (Amerhippus)andHippidionis less understood.

Results

Here, we use stable carbon and oxygen isotopes preserved in 67 fossil tooth and bone samples for seven species of horses from 25 different localities to document the magnitude of the dietary shifts of horses and ancient floral change during the Plio-Pleistocene. Dietary reconstructions inferred from stable isotopes of both genera of horses present in South America document dietary separation and environmental changes in ancient ecosystems, including C3/C4transitions. Stable isotope data demonstrate changes in C4grass consumption, inter-species dietary partitioning and variation in isotopic niche breadth of mixed feeders with latitudinal gradient.

Conclusions

The data forHippidionindicate a preference varying from C3plants to mixed C3-C4plants in their diet.Equus (Amerhippus)shows three different patterns of dietary partitioningEquus(A.)neogeusfrom the province of Buenos Aires indicate a preference for C3plants in the diet.Equus(A.)andiumfrom Ecuador andEquus(A.)insulatusfrom Bolivia show a preference for to a diet of mixed C3-C4plants, whileEquus(A.)santaeelenaefrom La Carolina (sea level of Ecuador) and Brazil are mostly C4feeders. These results confirm that ancient feeding ecology cannot always be inferred from dental morphology. While the carbon isotope composition of horses skeletal material decreased as latitude increased, we found evidence of boundary between a mixed C3/C4diet signal and a pure C4signal around 32° S and a change from a mixed diet signal to an exclusively C3signal around 35°S.

We found that the horses living at high altitudes and at low to middle latitude still have a C4component in their diet, except the specimens from 4000 m, which have a pure C3diet. The change in altitudinal vegetation gradients during the Pleistocene is one of several possibilities to explain the C4dietary component in horses living at high altitudes. Other alternative explanations imply that the horses fed partially at lower altitudes.
A model for the Escherichia coli FtsB/FtsL/FtsQ cell division complex
Authors: Villanelo Felipe , Ordenes Alexis , Brunet Juan , Lagos Rosalba , Monasterio Octavio
Published: June 2011

Background

Bacterial division is produced by the formation of a macromolecular complex in the middle of the cell, called the divisome, formed by more than 10 proteins. This process can be divided into two steps, in which the first is the polymerization of FtsZ to form the Z ring in the cytoplasm, and then the sequential addition of FtsA/ZipA to anchor the ring at the cytoplasmic membrane, a stage completed by FtsEX and FtsK. In the second step, the formation of the peptidoglycan synthesis machinery in the periplasm takes place, followed by cell division. The proteins involved in connecting both steps in cell division are FtsQ, FtsB and FtsL, and their interaction is a crucial and conserved event in the division of different bacteria. These components are small bitopic membrane proteins, and their specific function seems to be mainly structural. The purpose of this study was to obtain a structural model of the periplasmic part of the FtsB/FtsL/FtsQ complex, using bioinformatics tools and experimental data reported in the literature.

Results

Two oligomeric models for the periplasmic region of the FtsB/FtsL/FtsQ E. coli complex were obtained from bioinformatics analysis. The FtsB/FtsL subcomplex was modelled as a coiled-coil based on sequence information and several stoichiometric possibilities. The crystallographic structure of FtsQ was added to this complex, through protein-protein docking. Two final structurally-stable models, one trimeric and one hexameric, were obtained. The nature of the protein-protein contacts was energetically favourable in both models and the overall structures were in agreement with the experimental evidence reported.

Conclusions

The two models obtained for the FtsB/FtsL/FtsQ complex were stable and thus compatible with the in vivo periplasmic complex structure. Although the hexameric model 2:2:2 has features that indicate that this is the most plausible structure, the ternary complex 1:1:1 cannot be discarded. Both models could be further stabilized by the binding of the other proteins of the divisome. The bioinformatics modelling of this kind of protein complex, whose function is mainly structural, provide useful information. Experimental results should confirm or reject these models and provide new data for future bioinformatics studies to refine the models.