bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humanitarian welfare values in a changing social environment: A survey of social work undergraduate students in Beijing and Shanghai
Authors: Lou Vivian WQ , Pearson Veronica , Wong Yu C 
Published: November 2010

• Summary: Internationally accepted social work values are based on ideas about rights, social justice and equitable resource distribution. Does social work education in China embody similar values? Are these values influenced by culture and the current political/economic environment? The research posed three questions. Do social work students studying in metropolitan China support humanitarian welfare values? Are values affected by demographic backgrounds? Does social work education enhance humanitarian values? A self-administered, standardized questionnaire was distributed in 26 classes of social work students studying in seven universities in Beijing and Shanghai ( n = 1328). • Findings: Students do not support humanitarian welfare values strongly; and a decrease in these values was observed in senior students. Significant differences in values were found based on gender and on rural/urban origins. Female students were more likely to agree with humanitarian value statements; rural and urban students tended to agree more with values from which they had potential to benefit. • Applications: Social work knowledge and skills rather than values maybe more immediately relevant to Chinese society. However, independent professional practitioners need a solid foundation of professional values to inform practice and standardize the social work role. There needs to be an ongoing debate in China involving social work educators and practitioners about values and their relation to Chinese society, the ways in which they are influenced by non-Chinese cultures; and how to infuse these consistently into social work curricula in Chinese universities.
A community engagement orientation among people with a history of substance misuse and incarceration
Authors: Redman Dina 
Published: November 2010

• Summary: Community engagement, or acting on behalf of the collective, can provide a variety of rewards. Nonetheless, people who misuse substances are less likely to endorse such goals as making a contribution to society or correcting systemic inequities. As people modify their use of drugs or alcohol, they have been shown to draw purpose from community engagement. This mixed methods study examined contributors to a community engagement orientation among 68 respondents with a history of substance misuse and incarceration. • Findings: In the initial qualitative analysis, four themes emerged related to the respondents’ sense of purpose in life. The theme most frequently mentioned, community engagement, is the focus of this study. Discriminant analyses revealed that those endorsing community engagement goals were older at the onset of heavy drinking, more likely to have received public assistance, more highly educated, as were their mothers, manifested greater self-esteem, and had previously been involved in an organization addressing community concerns. • Applications: Social workers might assist clients in identifying and manifesting what they believe to be their purpose in life, with particular attention to community engagement. In this way, they may utilize the wisdom gained from challenging experiences to benefit others and bring about social change.
Aboriginal organizational response to the need for culturally appropriate services in three small Canadian cities
Authors: Sookraj Dixon , Hutchinson Peter , Evans Michael , Ann Murphy Mary ,   The Okanagan Urban Aboriginal Health Research Collective
Published: November 2010

• Summary: This component of a larger participatory qualitative case study investigated how urban Aboriginal human service organizations respond to the needs of the growing Aboriginal populations residing in three small cities in the Interior region of British Columbia, Canada. The study focused specifically on the challenges that the organizations experienced in delivering health and social services, and in facilitating access to mainstream services. Semi-structured interviews were conducted with eight senior administrators from seven urban Aboriginal organizations. • Findings: Participants reported numerous barriers to delivering adequate and culturally appropriate services. Their organizations were challenged to provide a complex array of services to a culturally diverse urban Aboriginal population. Moreover, these organizations operated in turbulent economic, institutional and political environments, which presented additional challenges in several areas: recruiting and retaining qualified Aboriginal staff; securing funding; meeting different and conflicting accountability requirements; using political influence; and linking with both mainstream organizations and local Aboriginal communities. • Applications: Fundamental tensions between the existing specialized and expert-based, mainstream system and Aboriginal service providers’ holistic approach to well-being are apparent. Implications for future research, policy and practice needed to promote the development of culturally appropriate and responsive services are discussed.
Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results
Authors: Kantarjian Hagop M. , Giles Francis J. , Bhalla Kapil N. , Pinilla-Ibarz Javier , Larson Richard A. , Gattermann Norbert , Ottmann Oliver G. , Hochhaus Andreas , Radich Jerald P. , Saglio Giuseppe , Hughes Timothy P. , Martinelli Giovanni , Kim Dong-Wook , Shou Yaping , Gallagher Neil J. , Blakesley Rick , Baccarani Michele , Cortes Jorge , le Coutre Philipp D. 
Published: November 2010

Abstract
Nilotinib is a potent selective inhibitor of the BCR-ABL tyrosine kinase approved for use in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP), and in CML-CP and CML-accelerated phase after imatinib failure. Nilotinib (400 mg twice daily) was approved on the basis of the initial results of this phase 2 open-label study. The primary study endpoint was the proportion of patients achieving major cytogenetic response (CyR). All patients were followed for ≥ 24 months or discontinued early. Of 321 patients, 124 (39%) continue on nilotinib treatment. Overall, 59% of patients achieved major CyR; this was complete CyR (CCyR) in 44%. Of patients achieving CCyR, 56% achieved major molecular response. CyRs were durable, with 84% of patients who achieved CCyR maintaining response at 24 months. The overall survival at 24 months was 87%. Adverse events were mostly mild to moderate, generally transient, and easily managed. This study indicates that nilotinib is effective, with a manageable safety profile, and can provide favorable long-term benefits for patients with CML-CP after imatinib failure. This trial was registered at www.clinicaltrials.gov as #NCT00109707.
Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the pathogenesis of mouse and human CLL
Authors: Chen Shih-Shih , Claus Rainer , Lucas David M. , Yu Lianbo , Qian Jiang , Ruppert Amy S. , West Derek A. , Williams Katie E. , Johnson Amy J. , Sablitzky Fred , Plass Christoph , Byrd John C. 
Published: November 2010

Abstract
Inhibitor of DNA binding protein 4 (ID4) is a member of the dominant-negative basic helix-loop-helix transcription factor family that lacks DNA binding activity and has tumor suppressor function. ID4 promoter methylation has been reported in acute myeloid leukemia and chronic lymphocytic leukemia (CLL), although the expression, function, and clinical relevance of this gene have not been characterized in either disease. We demonstrate that the promoter of ID4 is consistently methylated to various degrees in CLL cells, and increased promoter methylation in a univariable analysis correlates with shortened patient survival. However, ID4 mRNA and protein expression is uniformly silenced in CLL cells irrespective of the degree of promoter methylation. The crossing of ID4+/− mice with Eμ-TCL1 mice triggers a more aggressive murine CLL as measured by lymphocyte count and inferior survival. Hemizygous loss of ID4 in nontransformed TCL1-positive B cells enhances cell proliferation triggered by CpG oligonucleotides and decreases sensitivity to dexamethasone-mediated apoptosis. Collectively, this study confirms the importance of the silencing of ID4 in murine and human CLL pathogenesis.
Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity
Authors: Li Chia-Cheng , Ho Tin-Yun , Kao Chia-Hung , Wu Shih-Lu , Liang Ji-An , Hsiang Chien-Yun 
Published: November 2010

Abstract

Background
Sodium/iodide symporter (NIS) mediates the active transport and accumulation of iodide from the blood into the thyroid gland. His-226 located in the extracellular region of NIS has been demonstrated to be critical for iodide transport in our previous study. The conserved charged amino acid residues in the extracellular region of NIS were therefore characterized in this study.

Methods
Fourteen charged residues (Arg-9, Glu-79, Arg-82, Lys-86, Asp-163, His-226, Arg-228, Asp-233, Asp-237, Arg-239, Arg-241, Asp-311, Asp-322, and Asp-331) were replaced by alanine. Iodide uptake abilities of mutants were evaluated by steady-state and kinetic analysis. The three-dimensional comparative protein structure of NIS was further modeled using sodium/glucose transporter as the reference protein.

Results
All the NIS mutants were expressed normally in the cells and targeted correctly to the plasma membrane. However, these mutants, except R9A, displayed severe defects on the iodide uptake. Further kinetic analysis revealed that mutations at conserved positively charged amino acid residues in the extracellular region of NIS led to decrease NIS-mediated iodide uptake activity by reducing the maximal rate of iodide transport, while mutations at conserved negatively charged residues led to decrease iodide transport by increasing dissociation between NIS mutants and iodide.

Conclusions
This is the first report characterizing thoroughly the functional significance of conserved charged amino acid residues in the extracellular region of NIS. Our data suggested that conserved charged amino acid residues, except Arg-9, in the extracellular region of NIS were critical for iodide transport.
The role of HIF-1 in up-regulating MICA expression on human renal proximal tubular epithelial cells during hypoxia/reoxygenation
Authors: Luo Lei , Lu Jun , Wei Liang , Long Dan , Guo Jia Y , Shan Juan , Li Fu S , Lu Ping Y , Li Ping Y , Feng Li 
Published: November 2010

Abstract

Background
Human major histocompatibility complex class I-related chain A (MICA) plays a dual role in adaptive and innate immune responses. Increasing evidence demonstrates that MICA is closely correlated with acute and chronic kidney allograft rejection. Therefore, understanding the activation mechanisms of MICA is important in kidney transplantation. We previously demonstrated that ischemia/reperfusion injury (IRI) could up-regulate MICA expression on mouse kidney allografts. Since hypoxia-inducible factor-1 (HIF-1) is the master regulator of cellular adaptive responses to hypoxia during IRI, here we investigate whether HIF-1 could up-regulate MICA expression and its influence on NK cell cytotoxicity.

Results
We find that HIF-1alpha plays an important role in up-regulating MICA expression, inducing IFNgamma secretion and NK cell cytotoxicity during hypoxia/reoxygenation. First, we generated a HIF-1alphaDELTAODD-expressing adenovirus to stably and functionally express HIF-1alpha in human renal proximal tubular epithelial (HK-2) cells under normoxia conditions. HIF-1alpha over-expression in HK-2 cells induces MICA expression and enhances NK cell cytotoxic activity towards cells that express HIF-1alpha. Second, we used a hypoxia/reoxygenation cell model to simulate IRI in vitro and found that the suppression of HIF-1alpha by RNAi induces down-regulation of MICA expression and inhibits NK cytotoxicity. In antibody blocking experiments, an anti-MICA mAb was able to down-regulate NK cell cytotoxic activity towards HK-2 cells that over-expressed HIF-1alpha. Moreover, when NK cells were co-cultured with the HK-2 cells expressing MICA, which was up-regulated by over-expression of HIF-1alpha, there was a significant increase in the secretion of IFNgamma. In the presence of the blocking MICA mAb, IFNgamma secretion was significantly decreased.

Conclusions
These results demonstrate that hypoxia/reoxygenation-promoted MICA expression on HK-2 cells is through a HIF-1 pathway. The increased IFNgamma secretion and enhanced NK cell cytotoxicity was mainly due to the surface expression of MICA induced by over-expression of HIF-1alpha. This study enhances our understanding of MICA activation mechanisms during kidney transplantation and provides insights into how IRI can influence transplant outcome. Moreover, these findings might be also important for developing strategies to reduce the effect of MICA in kidney transplant outcomes in the future.
Imprinted genes show unique patterns of sequence conservation
Authors: Hutter Barbara , Bieg Matthias , Helms Volkhard , Paulsen Martina 
Published: November 2010

Abstract

Background
Genomic imprinting is an evolutionary conserved mechanism of epigenetic gene regulation in placental mammals that results in silencing of one of the parental alleles. In order to decipher interactions between allele-specific DNA methylation of imprinted genes and evolutionary conservation, we performed a genome-wide comparative investigation of genomic sequences and highly conserved elements of imprinted genes in human and mouse.

Results
Evolutionarily conserved elements in imprinted regions differ from those associated with autosomal genes in various ways. Whereas for maternally expressed genes strong divergence of protein-encoding sequences is most prominent, paternally expressed genes exhibit substantial conservation of coding and noncoding sequences. Conserved elements in imprinted regions are marked by enrichment of CpG dinucleotides and low (TpG+CpA)/(2·CpG) ratios indicate reduced CpG deamination. Interestingly, paternally and maternally expressed genes can be distinguished by differences in G+C and CpG contents that might be associated with unusual epigenetic features. Especially noncoding conserved elements of paternally expressed genes are exceptionally G+C and CpG rich. In addition, we confirmed a frequent occurrence of intronic CpG islands and observed a decelerated degeneration of ancient LINE-1 repeats. We also found a moderate enrichment of YY1 and CTCF binding sites in imprinted regions and identified several short sequence motifs in highly conserved elements that might act as additional regulatory elements.

Conclusions
We discovered several novel conserved DNA features that might be related to allele-specific DNA methylation. Our results hint at reduced CpG deamination rates in imprinted regions, which affects mostly noncoding conserved elements of paternally expressed genes. Pronounced differences between maternally and paternally expressed genes imply specific modes of evolution as a result of differences in epigenetic features and a special response to selective pressure. In addition, our data support the potential role of intronic CpG islands as epigenetic key regulatory elements and suggest that evolutionary conserved LINE-1 elements fulfill regulatory functions in imprinted regions.
Transcriptome analysis of a barley breeding program examines gene expression diversity and reveals target genes for malting quality improvement
Authors: Muñoz-Amatriaín María , Xiong Yanwen , Schmitt Mark R , Bilgic Hatice , Budde Allen D , Chao Shiaoman , Smith Kevin P , Muehlbauer Gary J 
Published: November 2010

AbstractBackgroundAdvanced cycle breeding utilizes crosses among elite lines and is a successful method to develop new inbreds. However, it results in a reduction in genetic diversity within the breeding population. The development of malting barley varieties requires the adherence to a narrow malting quality profile and thus the use of advanced cycle breeding strategies. Although attention has been focused on diversity in gene expression and its association with genetic diversity, there are no studies performed in a single breeding program examining the implications that consecutive cycles of breeding have on gene expression variation and identifying the variability still available for future improvement.ResultsFifteen lines representing the historically important six-rowed malting barley breeding program of the University of Minnesota were genotyped with 1,524 SNPs, phenotypically examined for six malting quality traits, and analyzed for transcript accumulation during germination using the Barley1 GeneChip array. Significant correlation was detected between genetic and transcript-level variation. We observed a reduction in both genetic and gene expression diversity through the breeding process, although the expression of many genes have not been fixed. A high number of quality-related genes whose expression was fixed during the breeding process was identified, indicating that much of the diversity reduction was associated with the improvement of the complex phenotype "malting quality", the main goal of the University of Minnesota breeding program. We also identified 49 differentially expressed genes between the most recent lines of the program that were correlated with one or more of the six primary malting quality traits. These genes constitute potential targets for the improvement of malting quality within the breeding program.ConclusionsThe present study shows the repercussion of advanced cycle breeding on gene expression diversity within an important barley breeding program. A reduction in gene expression diversity was detected, although there is diversity still present after forty years of breeding that can exploited for future crop improvement. In addition, the identification of candidate genes for enhancing malting quality may be used to optimize the selection of targets for further improvements in this economically important phenotype.
TGF-β-induced growth inhibition in B-cell lymphoma correlates with Smad1/5 signalling and constitutively active p38 MAPK
Authors: Bakkebø Maren , Huse Kanutte , Hilden Vera I , Smeland Erlend B , Oksvold Morten P 
Published: November 2010

Abstract

Background
Cytokines of the transforming growth factor β (TGF-β) superfamily exert effects on proliferation, apoptosis and differentiation in various cell types. Cancer cells frequently acquire resistance to the anti-proliferative signals of TGF-β, which can be due to mutations in proteins of the signalling cascade. We compared the TGF-β-related signalling properties in B-cell lymphoma cell lines that were sensitive or resistant to TGF-β-induced anti-proliferative effects.

Results
TGF-β sensitive cell lines expressed higher cell surface levels of the activin receptor-like kinase 5 (Alk-5), a TGF-β receptor type 1. The expression levels of the other TGF-β and bone morphogenetic protein receptors were comparable in the different cell lines. TGF-β-induced phosphorylation of Smad2 was similar in TGF-β sensitive and resistant cell lines. In contrast, activation of Smad1/5 was restricted to cells that were sensitive to growth inhibition by TGF-β. Moreover, with activin A we detected limited anti-proliferative effects, strong phosphorylation of Smad2, but no Smad1/5 phosphorylation. Up-regulation of the TGF-β target genes Id1 and Pai-1 was identified in the TGF-β sensitive cell lines. Constitutive phosphorylation of MAPK p38 was restricted to the TGF-β sensitive cell lines. Inhibition of p38 MAPK led to reduced sensitivity to TGF-β.

Conclusions
We suggest that phosphorylation of Smad1/5 is important for the anti-proliferative effects of TGF-β in B-cell lymphoma. Alk-5 was highly expressed in the sensitive cell lines, and might be important for signalling through Smad1/5. Our results indicate a role for p38 MAPK in the regulation of TGF-β-induced anti-proliferative effects.
Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage
Authors: Ogetii Gilbert N , Akech Samuel , Jemutai Julie , Boga Mwanamvua , Kivaya Esther , Fegan Greg , Maitland Kathryn 
Published: November 2010

Abstract

Background
Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence.

Methods
Retrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded.

Results
954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01.

Conclusion
There was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.